AccScience Publishing / ITPS / Online First / DOI: 10.36922/itps.1726
Cite this article
636
Download
2304
Views
Journal Browser
Volume | Year
Issue
Search
News and Announcements
View All
REVIEW

Mitochondria: The master regulator of aging

Pouya Sarvari1* Pourya Sarvari1
Show Less
1 Iran National Elite Foundation (INEF), Tehran, Iran
INNOSC Theranostics and Pharmacological Sciences, 1726 https://doi.org/10.36922/itps.1726
Submitted: 31 August 2023 | Accepted: 16 November 2023 | Published: 22 February 2024
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC BY-NC 4.0) ( https://creativecommons.org/licenses/by-nc/4.0/ )
Abstract

Mitochondria are ATP-producing organelles in eukaryotic organisms that serve as the cell’s power plants. Besides, mitochondria are integral to regulating cellular homeostasis and metabolism as a result of their essential roles in reactive oxygen species (ROS) production, bioenergetics, catabolism and anabolism, heme and iron-sulfur biosynthesis, iron and calcium homeostasis, apoptosis and signal transduction, as well as immunity and inflammation. It is well accepted that mitochondria are evolutionarily derived from endosymbiotic alphaproteobacteria within eukaryotic cells adapted for effective energy transduction. Although most of the mitochondrial DNA (mtDNA) is thought to have been transported to the eukaryotic nucleus during evolution, mitochondria may have preserved protein-coding genes within their own DNA. Accumulating data show that a progressive decline of mitochondria regulates aging. The present review aims to outline the role of mitochondria in various aspects of aging, including unfolded protein response, generation of ROS, and the contribution of somatic mtDNA mutations as well as inflammation in aging. Moreover, we propose mitochondria-targeted nanoparticles and mitochondrial genome editing as novel tools to modify mitochondrial genome aberrations.

Keywords
Aging
Heteroplasmy
Mitochondrial DNA
Mitochondrial genome editing
Mitochondrial quality control
Mitochondria-targeted nanoparticles
Mitochondrial unfolded protein response
Reactive oxygen species
Funding
None.
References
  1. Flatt TJ. A new definition of aging? Front Genet. 2012;3:148. doi: 10.3389/fgene.2012.00148

 

  1. Liguori I, Russo G, Curcio F, et al. Oxidative stress, aging, and diseases. Clin Interv Aging. 2018:757-772. doi: 10.2147/cia.s158513

 

  1. López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell. 2013;153(6):1194-1217. doi: 10.1016/j.cell.2013.05.039

 

  1. Petersen KF, Befroy D, Dufour S, et al. Mitochondrial dysfunction in the elderly: Possible role in insulin resistance. Science. 2003;300(5622):1140-1142. doi: 10.1126/science.1082889

 

  1. Pagiatakis C, Musolino E, Gornati R, Bernardini G, Papait R. Epigenetics of aging and disease: A brief overview. Aging Clin Exp Res. 2021;33:737-745. doi: 10.1007/s40520-019-01430-0

 

  1. Zhang S, Zhu N, Gu J, et al. Crosstalk between lipid rafts and aging: New frontiers for delaying aging. Aging Dis. 2022;13(4):1042. doi: 10.14336/ad.2022.0116

 

  1. Roger AJ, Muñoz-Gómez SA, Kamikawa R. The origin and diversification of mitochondria. Curr Biol. 2017;27(21):R1177-R1192. doi: 10.1016/j.cub.2017.09.015

 

  1. Cavalier-Smith T. Origin of mitochondria by intracellular enslavement of a photosynthetic purple bacterium. Proc Biol Sci. 2006;273(1596):1943-1952. doi: 10.1098/rspb.2006.3531

 

  1. Brown WM, George M Jr., Wilson AC. Rapid evolution of animal mitochondrial DNA. Proc Natl Acad Sci U S A. 1979;76(4):1967-1971. doi: 10.1073/pnas.76.4.1967

 

  1. Lax NZ, Turnbull DM, Reeve AK. Mitochondrial mutations: Newly discovered players in neuronal degeneration. Neuroscientist. 2011;17(6):645-658. doi: 10.1177/1073858411385469

 

  1. Ng MYW, Wai T, Simonsen A. Quality control of the mitochondrion. Dev Cell. 2021;56(7):881-905. doi: 10.1016/j.devcel.2021.02.009

 

  1. Patananan AN, Sercel AJ, Teitell MA. More than a powerplant: The influence of mitochondrial transfer on the epigenome. Curr Opin Physiol. 2018;3:16-24. doi: 10.1016/j.cophys.2017.11.006

 

  1. Ryan MT, Hoogenraad NJ. Mitochondrial-nuclear communications. Annu Rev Biochem. 2007;76:701-722. doi: 10.1146/annurev.biochem.76.052305.091720

 

  1. Singh B, Modica-Napolitano JS, Singh KK. Defining the Momiome: Promiscuous Information Transfer by Mobile Mitochondria and the Mitochondrial Genome. Netherlands: Elsevier; 2017. p. 1-17. doi: 10.1016/j.semcancer.2017.05.004

 

  1. Pugh TD, Conklin MW, Evans TD, et al. A shift in energy metabolism anticipates the onset of sarcopenia in rhesus monkeys. Aging Cell. 2013;12(4):672-681. doi: 10.1111/acel.12091

 

  1. Nunnari J, Suomalainen A. Mitochondria: In sickness and in health. Cell. 2012;148(6):1145-1159. doi: 10.1016/j.cell.2012.02.035

 

  1. Giles RE, Blanc H, Cann HM, Wallace DC. Maternal inheritance of human mitochondrial DNA. Proc Natl Acad Sci U S A. 1980;77(11):6715-6719. doi: 10.1073/pnas.77.11.6715

 

  1. Wallace DC, Chalkia D. Mitochondrial DNA genetics and the heteroplasmy conundrum in evolution and disease. Cold Spring Harb Perspect Biol. 2013;5(11):a021220. doi: 10.1101/cshperspect.a021220

 

  1. Gyllensten U, Wharton D, Josefsson A, Wilson AC. Paternal inheritance of mitochondrial DNA in mice. Nature. 1991;352(6332):255-257. doi: 10.1038/352255a0

 

  1. Schwartz M, Vissing J. Paternal inheritance of mitochondrial DNA. N Engl J Med. 2002;347(8):576-580. doi: 10.1056/nejmoa020350

 

  1. Kvist L, Martens J, Nazarenko AA, Orell M. Paternal leakage of mitochondrial DNA in the great tit (Parus major). Mol Biol Evol. 2003;20(2):243-247. doi: 10.1093/molbev/msg025

 

  1. Satoh M, Kuroiwa T. Organization of multiple nucleoids and DNA molecules in mitochondria of a human cell. Exp Cell Res. 1991;196(1):137-140. doi: 10.1016/0014-4827(91)90467-9

 

  1. Lee SR, Han J. Mitochondrial nucleoid: Shield and switch of the mitochondrial genome. Oxid Med Cell Longev. 2017;2017:8060949. doi: 10.1155/2017/8060949

 

  1. Legros F, Malka F, Frachon P, Lombès A, Rojo M. Organization and dynamics of human mitochondrial DNA. J Cell Sci. 2004;117(13):2653-2662. doi: 10.1242/jcs.01134

 

  1. Kukat C, Wurm CA, Spåhr H, Falkenberg M, Larsson NG, Jakobs S. Super-resolution microscopy reveals that mammalian mitochondrial nucleoids have a uniform size and frequently contain a single copy of mtDNA. Proc Natl Acad Sci. 2011;108(33):13534-13539. doi: 10.1073/pnas.1109263108

 

  1. Sasaki T, Sato Y, Higashiyama T, Sasaki N. Live imaging reveals the dynamics and regulation of mitochondrial nucleoids during the cell cycle in Fucci2-HeLa cells. Sci Rep. 2017;7(1):11257. doi: 10.1038/s41598-017-10843-8

 

  1. Iborra FJ, Kimura H, Cook P. The functional organization of mitochondrial genomes in human cells. BMC Biol. 2004;2:9. doi: 10.1186/1741-7007-2-9

 

  1. Tauber J, Dlasková A, Šantorová J, et al. Distribution of mitochondrial nucleoids upon mitochondrial network fragmentation and network reintegration in HEPG2 cells. Int J Biochem Cell Biol. 2013;45(3):593-603. doi: 10.1016/j.biocel.2012.11.019

 

  1. Jajoo R, Jung Y, Huh D, et al. Accurate concentration control of mitochondria and nucleoids. Science. 2016;351(6269):169-172. doi: 10.1126/science.aaa8714

 

  1. Rajala N, Gerhold JM, Martinsson P, Klymov A, Spelbrink JN. Replication factors transiently associate with mtDNA at the mitochondrial inner membrane to facilitate replication. Nucleic Acids Res. 2013;42(2):952-967. doi: 10.1093/nar/gkt988

 

  1. Garrido N, Griparic L, Jokitalo E, Wartiovaara J, van der Bliek AM, Spelbrink JN. Composition and dynamics of human mitochondrial nucleoids. Mol Biol Cell. 2003;14(4):1583-1596. doi: 10.1091/mbc.e02-07-0399

 

  1. Bouda E, Stapon A, Garcia‐Diaz M. Mechanisms of mammalian mitochondrial transcription. Protein Sci. 2019;28(9):1594-1605. doi: 10.1002/pro.3688

 

  1. Yu R, Lendahl U, Nistér M, Zhao J. Regulation of mammalian mitochondrial dynamics: Opportunities and challenges. Front Endocrinol (Lausanne). 2020;11:374. doi: 10.3389/fendo.2020.00374

 

  1. Bulthuis EP, Adjobo-Hermans MJW, Willems PHGM, Koopman WJH. Mitochondrial morphofunction in mammalian cells. Antioxid Redox Signal. 2019;30:2066-2109. doi: 10.1089/ars.2018.7534

 

  1. Stojanovski D, Johnston AJ, Streimann I, Hoogenraad NJ, Ryan MT. Import of nuclear-encoded proteins into mitochondria. Exp Physiol. 2003;88(1):57-64. doi: 10.1113/eph8802501

 

  1. Walker BR, Moraes CT. Nuclear-mitochondrial interactions. Biomolecules. 2022;12(3):427. doi: 10.3390/biom12030427

 

  1. Shokolenko IN, Alexeyev MF. Mitochondrial transcription in mammalian cells. Front Biosci (Landmark Ed). 2017;22:835. doi: 10.2741/4520

 

  1. Wallace DC. A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: A dawn for evolutionary medicine. Annu Rev Genet. 2005;39:359-407. doi: 10.1146/annurev.genet.39.110304.095751

 

  1. Taanman JW. The mitochondrial genome: Structure, transcription, translation and replication. Biochim Biophys Acta. 1999;1410(2):103-123. doi: 10.1016/s0005-2728(98)00161-3

 

  1. Chan SSL, Copeland WC. DNA polymerase gamma and mitochondrial disease: Understanding the consequence of POLG mutations. Biochim Biophys Acta. 2009;1787(5):312-319. doi: 10.1016/j.bbabio.2008.10.007

 

  1. Asahara H, Li Y, Fuss J, et al. Stimulation of human DNA polymerase ϵ by MDM2. Nucleic Acids Res. 2003;31(9):2451-2459. doi: 10.1093/nar/gkg342

 

  1. Shcherbakova PV, Bebenek K, Kunkel TA. Functions of eukaryotic DNA polymerases. Sci Aging Knowledge Environ. 2003;2003(8):RE3. doi: 10.1126/sageke.2003.8.re3

 

  1. Druzhyna NM, Wilson GL, LeDoux SP. Mitochondrial DNA repair in aging and disease. Mech Ageing Dev. 2008;129(7-8):383-390. doi: 10.1016/j.mad.2008.03.002

 

  1. Yakes FM, Van Houten B. Mitochondrial DNA damage is more extensive and persists longer than nuclear DNA damage in human cells following oxidative stress. Proc Natl Acad Sci U S A. 1997;94(2):514-519. doi: 10.1073/pnas.94.2.514

 

  1. Ide T, Tsutsui H, Hayashidani S, et al. Mitochondrial DNA damage and dysfunction associated with oxidative stress in failing hearts after myocardial infarction. Circ Res. 2001;88(5):529-535. doi: 10.1161/01.res.88.5.529

 

  1. Larsen NB, Rasmussen M, Rasmussen LJ. Nuclear and mitochondrial DNA repair: Similar pathways? Mitochondrion 2005;5(2):89-108. doi: 10.1016/j.mito.2005.02.002

 

  1. Bohr VA, Dianov GL. Oxidative DNA damage processing in nuclear and mitochondrial DNA. Biochimie. 1999;81(1-2):155-160. doi: 10.1016/S0300-9084(99)80048-0

 

  1. Hamilton ML, Van Remmen H, Drake JA, et al. Does oxidative damage to DNA increase with age? Proc Natl Acad Sci U S A. 2001;98(18):10469-10474. doi: 10.1073/pnas.171202698

 

  1. Catalán M, Olmedo I, Faúndez J, Jara JA. Medicinal chemistry targeting mitochondria: From new vehicles and pharmacophore groups to old drugs with mitochondrial activity. Int J Mol Sci. 2020;21(22):8684. doi: 10.3390/ijms21228684

 

  1. Singer TP, Ramsay RR. Mechanism of the neurotoxicity of MPTP: An update. FEBS Lett. 1990;274(1-2):1-8. doi: 10.1016/0014-5793(90)81315-f

 

  1. Cho H, Cho YY, Shim MS, Lee JY, Lee HS, Kang HC. Mitochondria-targeted drug delivery in cancers. Biochim Biophys Acta Mol Basis Dis. 2020;1866(8):165808. doi: 10.1016/j.bbadis.2020.165808

 

  1. Filograna R, Mennuni M, Alsina D, Larsson NG. Mitochondrial DNA copy number in human disease: The more the better? FEBS Lett. 2021;595(8):976-1002. doi: 10.1002/1873-3468.14021

 

  1. Kong M, Guo L, Xu W, et al. Aging-associated accumulation of mitochondrial DNA mutations in tumor origin. Life Med. 2022;1(2):149-167. doi: 10.1093/lifemedi/lnac014

 

  1. Rossignol R, Malgat M, Mazat JP, Letellier T. Threshold effect and tissue specificity: Implication for mitochondrial cytopathies. J Biol Chem. 1999;274(47):33426-33432. doi: 10.1074/jbc.274.47.33426

 

  1. Rossignol R, Faustin B, Rocher C, Malgat M, Mazat JP, Letellier T. Mitochondrial threshold effects. Biochem J. 2003;370(3):751-762. doi: 10.1042/bj20021594

 

  1. Sanchez-Contreras M, Kennedy SR. The complicated nature of somatic mtDNA mutations in aging. Front Aging. 2022;2:805126. doi: 10.3389/fragi.2021.805126

 

  1. Stewart JB, Chinnery PF. The dynamics of mitochondrial DNA heteroplasmy: Implications for human health and disease. Nat Rev Genet. 2015;16(9):530-542. doi: 10.1038/nrg3966

 

  1. Filograna R, Koolmeister C, Upadhyay M, et al. Modulation of mtDNA copy number ameliorates the pathological consequences of a heteroplasmic mtDNA mutation in the mouse. Sci Adv. 2019;5(4):eaav9824. doi: 10.1126/sciadv.aav9824

 

  1. Mancuso M, Orsucci D, Angelini C, et al. The m. 3243A> G mitochondrial DNA mutation and related phenotypes. A matter of gender? J Neurol. 2014;261:504-510. doi: 10.1007/s00415-013-7225-3

 

  1. Li D, Liang C, Zhang T, et al. Pathogenic mitochondrial DNA 3243A> G mutation: From genetics to phenotype. Front Genet. 2022;13:951185. doi: 10.3389/fgene.2022.951185

 

  1. Goto Y, Nonaka I, Horai S. A mutation in the tRNALeu (UUR) gene associated with the MELAS subgroup of mitochondrial encephalomyopathies. Nature. 1990;348(6302):651-653. doi: 10.1038/348651a0

 

  1. Arbeithuber B, Cremona MA, Hester J, et al. Advanced age increases frequencies of de novo mitochondrial mutations in macaque oocytes and somatic tissues. Proc Natl Acad Sci U S A. 2022;119(15):e2118740119. doi: 10.1073/pnas.2118740119

 

  1. Cortopassi GA, Arnheim N. Detection of a specific mitochondrial DNA deletion in tissues of older humans. Nucleic Acids Res. 1990;18(23):6927-6933. doi: 10.1093/nar/18.23.6927

 

  1. Pikó L, Hougham AJ, Bulpitt KJ. Studies of sequence heterogeneity of mitochondrial DNA from rat and mouse tissues: Evidence for an increased frequency of deletions/ additions with aging. Mech Ageing Dev. 1988;43(3):279-293. doi: 10.1016/0047-6374(88)90037-1

 

  1. Khrapko K, Vijg J. Mitochondrial DNA mutations and aging: Devils in the details? Trends Genet. 2009;25(2):91-98. doi: 10.1016/j.tig.2008.11.007

 

  1. Kujoth GC, Hiona A, Pugh TD, et al. Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging. Science. 2005;309(5733):481-484. doi: 10.1126/science.1112125

 

  1. Trifunovic A, Wredenberg A, Falkenberg M, et al. Premature ageing in mice expressing defective mitochondrial DNA polymerase. Nature. 2004;429(6990):417-423. doi: 10.1038/nature02517

 

  1. Bailey LJ, Cluett TJ, Reyes A, et al. Mice expressing an error-prone DNA polymerase in mitochondria display elevated replication pausing and chromosomal breakage at fragile sites of mitochondrial DNA. Nucleic Acids Res. 2009;37(7):2327-2335. doi: 10.1093/nar/gkp091

 

  1. Williams SL, Huang J, Edwards YJK, et al. The mtDNA mutation spectrum of the progeroid Polg mutator mouse includes abundant control region multimers. Cell Metab. 2010;12(6):675-682. doi: 10.1016/j.cmet.2010.11.012

 

  1. Harman D. Aging: A theory based on free radical and radiation chemistry. J Gerontol. 1956;11(3):298-300. doi: 10.1093/geronj/11.3.298

 

  1. Bandy B, Davison AJ. Mitochondrial mutations may increase oxidative stress: Implications for carcinogenesis and aging? Free Radic Biol Med. 1990;8(6):523-539. doi: 10.1016/0891-5849(90)90152-9

 

  1. Hiona A, Leeuwenburgh C. The role of mitochondrial DNA mutations in aging and sarcopenia: Implications for the mitochondrial vicious cycle theory of aging. Exp Gerontol. 2008;43(1):24-33. doi: 10.1016/j.exger.2007.10.001

 

  1. Alexeyev MF, Ledoux SP, Wilson GL. Mitochondrial DNA and aging. Clin Sci (Lond). 2004;107(4):355-364. doi: 10.1042/cs20040148

 

  1. Blagosklonny MV. Aging: Ros or tor. Cell Cycle. 2008;7(21):3344-3354. doi: 10.4161/cc.7.21.6965

 

  1. Cabreiro F, Ackerman D, Doonan R, et al. Increased life span from overexpression of superoxide dismutase in Caenorhabditis elegans is not caused by decreased oxidative damage. Free Radic Biol Med. 2011;51(8):1575-1582. doi: 10.1016/j.freeradbiomed.2011.07.020

 

  1. Gems D, Doonan R. Antioxidant defense and aging in C. elegans: Is the oxidative damage theory of aging wrong? Cell Cycle. 2009;8(11):1681-1687. doi: 10.4161/cc.8.11.8595

 

  1. Koc A, Gasch AP, Rutherford JC, Kim HY, Gladyshev VN. Methionine sulfoxide reductase regulation of yeast lifespan reveals reactive oxygen species-dependent and-independent components of aging. Proc Natl Acad Sci U S A. 2004;101(21):7999-8004. doi: 10.1073/pnas.0307929101

 

  1. Lapointe J, Hekimi S. When a theory of aging ages badly. Cell Mol Life Sci. 2010;67:1-8. doi: 10.1007/s00018-009-0138-8

 

  1. Mockett RJ, Sohal BH, Sohal RS. Expression of multiple copies of mitochondrially targeted catalase or genomic Mn superoxide dismutase transgenes does not extend the life span of Drosophila melanogaster. Free Radic Biol Med. 2010;49(12):2028-2031. doi: 10.1016/j.freeradbiomed.2010.09.029

 

  1. Pérez VI, Van Remmen H, Bokov A, Epstein CJ, Vijg J, Richardson A. The overexpression of major antioxidant enzymes does not extend the lifespan of mice. Aging Cell. 2009;8(1):73-75. doi: 10.15252/emmm.201708084

 

  1. Speakman JR, Selman C. The free‐radical damage theory: Accumulating evidence against a simple link of oxidative stress to ageing and lifespan. Bioessays. 2011;33(4):255-259. doi: 10.1002/bies.201000132

 

  1. Van Raamsdonk JM, Hekimi S. Superoxide dismutase is dispensable for normal animal lifespan. Proc Natl Acad Sci U S A. 2012;109(15):5785-5790. doi: 10.1073/pnas.1116158109

 

  1. Ristow M, Schmeisser S. Extending life span by increasing oxidative stress. Free Radic Biol Med. 2011;51(2):327-336. doi: 10.1016/j.freeradbiomed.2011.05.010

 

  1. Zarse K, Schmeisser S, Groth M, et al. Impaired insulin/IGF1 signaling extends life span by promoting mitochondrial L-proline catabolism to induce a transient ROS signal. Cell Metab. 2012;15(4):451-465. doi: 10.1016/j.cmet.2012.02.013

 

  1. Katayama M, Tanaka M, Yamamoto H, Ohbayashi T, Nimura Y, Ozawa T. Deleted mitochondrial DNA in the skeletal muscle of aged individuals. Biochem Int. 1991;25(1):47-56. doi: 10.1016/j.mito.2005.02.002

 

  1. Brierley EJ, Johnson MA, Lightowlers RN, James OF, Turnbull DM. Role of mitochondrial DNA mutations in human aging: Implications for the central nervous system and muscle. Ann Neurol. 1998;43(2):217-223. doi: 10.1002/ana.410430212

 

  1. Trifunovic A, Hansson A, Wredenberg A, et al. Somatic mtDNA mutations cause aging phenotypes without affecting reactive oxygen species production. Proc Natl Acad Sci U S A. 2005;102(50):17993-17998. doi: 10.1073/pnas.0508886102

 

  1. Shokolenko I, Venediktova N, Bochkareva A, Wilson GL, Alexeyev MF. Oxidative stress induces degradation of mitochondrial DNA. Nucleic Acids Res. 2009;37(8):2539-2548. doi: 10.1093/nar/gkp100

 

  1. Kennedy SR, Salk JJ, Schmitt MW, Loeb LA. Ultra-sensitive sequencing reveals an age-related increase in somatic mitochondrial mutations that are inconsistent with oxidative damage. PLoS Genet. 2013;9(9):e1003794. doi: 10.1371/journal.pgen.1003794

 

  1. Arbeithuber B, Hester J, Cremona MA, et al. Age-related accumulation of de novo mitochondrial mutations in mammalian oocytes and somatic tissues. PLoS Biol. 2020;18(7):e3000745. doi: 10.1371/journal.pbio.3000745

 

  1. Li H, Shen L, Hu P, et al. Aging-associated mitochondrial DNA mutations alter oxidative phosphorylation machinery and cause mitochondrial dysfunctions. Biochim Biophys Acta Mol Basis Dis. 2017;1863(9):2266-2273. doi: 10.1016/j.bbadis.2017.05.022

 

  1. Schroeder P, Gremmel T, Berneburg M, Krutmann J. Partial depletion of mitochondrial DNA from human skin fibroblasts induces a gene expression profile reminiscent of photoaged skin. J Invest Dermatol. 2008;128(9):2297-2303. doi: 10.1038/jid.2008.57

 

  1. Fukui H, Moraes CT. Mechanisms of formation and accumulation of mitochondrial DNA deletions in aging neurons. Hum Mol Genet. 2009;18(6):1028-1036. doi: 10.1093/hmg/ddn437

 

  1. Moreno-Gonzalez I, Soto C. Misfolded protein aggregates: Mechanisms, structures and potential for disease transmission. Semin Cell Dev Biol 2011;22:482-7.

 

  1. Haynes CM, Ron D. The mitochondrial UPR-protecting organelle protein homeostasis. J Cell Sci. 2010;123(22):3849-3855. doi: 10.1242/jcs.075119

 

  1. Pellegrino MW, Nargund AM, Haynes CM. Signaling the mitochondrial unfolded protein response. Biochim Biophys Acta. 2013;1833(2):410-416. doi: 10.1016/j.bbamcr.2012.02.019

 

  1. Bukau B, Weissman J, Horwich A. Molecular chaperones and protein quality control. Cell. 2006;125(3):443-451. doi: 10.1016/j.cell.2006.04.014

 

  1. Chacinska A, Koehler CM, Milenkovic D, Lithgow T, Pfanner N. Importing mitochondrial proteins: Machineries and mechanisms. Cell. 2009;138(4):628-644. doi: 10.1016/j.cell.2009.08.005

 

  1. Bie AS, Cömert C, Körner R, et al. An inventory of interactors of the human HSP60/HSP10 chaperonin in the mitochondrial matrix space. Cell Stress Chaperones. 2020;25:407-416. doi: 10.1007/s12192-020-01080-6

 

  1. Zhou C, Sun H, Zheng C, et al. Oncogenic HSP60 regulates mitochondrial oxidative phosphorylation to support Erk1/2 activation during pancreatic cancer cell growth. Cell Death Dis. 2018;9(2):161. doi: 10.1038/s41419-017-0196-z

 

  1. Craig EA. Hsp70 at the membrane: Driving protein translocation. BMC Biol. 2018;16(1):11. doi: 10.1186/s12915-017-0474-3

 

  1. Scherer PE, Krieg UC, Hwang ST, Vestweber D, Schatz G. A precursor protein partly translocated into yeast mitochondria is bound to a 70 kd mitochondrial stress protein. EMBO J. 1990;9(13):4315-4322. doi: 10.1002/j.1460-2075.1990.tb07880.x

 

  1. Ostermann J, Voos W, Kang PJ, Craig EA, Neupert W, Pfanner N. Precursor proteins in transit through mitochondrial contact sites interact with hsp70 in the matrix. FEBS Lett. 1990;277(1-2):281-284. doi: 10.1016/0014-5793(90)80865-g

 

  1. Liu Q, Krzewska J, Liberek K, Craig EA. Mitochondrial Hsp70 Ssc1: Role in protein folding. J Biol Chem. 2001;276(9):6112-6118. doi: 10.1074/jbc.m009519200

 

  1. Pimenta de Castro I, Costa A, Lam D, et al. Genetic analysis of mitochondrial protein misfolding in Drosophila melanogaster. Cell Death Differ. 2012;19(8):1308-1316. doi: 10.1038/cdd.2012.5

 

  1. Nargund AM, Pellegrino MW, Fiorese CJ, Baker BM, Haynes CM. Mitochondrial import efficiency of ATFS-1 regulates mitochondrial UPR activation. Science. 2012;337(6094):587-590. doi: 10.1126/science.1223560

 

  1. Qureshi MA, Haynes CM, Pellegrino M. The mitochondrial unfolded protein response: Signaling from the powerhouse. J Biol Chem. 2017;292(33):13500-13506. doi: 10.1074/jbc.r117.791061

 

  1. Runkel ED, Liu S, Baumeister R, Schulze E. Surveillance-activated defenses block the ROS–induced mitochondrial unfolded protein response. PLoS Genet. 2013;9(3):e1003346. doi: 10.1371/journal.pgen.1003346

 

  1. Fiorese CJ, Schulz AM, Lin YF, Rosin N, Pellegrino MW, Haynes CM. The transcription factor ATF5 mediates a mammalian mitochondrial UPR. Curr Biol. 2016;26(15):2037-2043. doi: 10.1016/j.cub.2016.06.002

 

  1. Gao K, Li Y, Hu S, Liu Y. SUMO peptidase ULP-4 regulates mitochondrial UPR-mediated innate immunity and lifespan extension. Elife. 2019;8:e41792. doi: 10.7554/elife.41792

 

  1. Haynes CM, Yang Y, Blais SP, Neubert TA, Ron D. The matrix peptide exporter HAF-1 signals a mitochondrial UPR by activating the transcription factor ZC376. 7 in C. elegans. Mol Cell. 2010;37(4):529-540. doi: 10.1016/j.molcel.2010.01.015

 

  1. Tran HC, Van Aken O. Mitochondrial unfolded protein-related responses across kingdoms: Similar problems, different regulators. Mitochondrion. 2020;53:166-177. doi: 10.1016/j.mito.2020.05.009

 

  1. Wrobel L, Topf U, Bragoszewski P, et al. Mistargeted mitochondrial proteins activate a proteostatic response in the cytosol. Nature. 2015;524(7566):485-488. doi: 10.1016/j.nbd.2009.08.009

 

  1. Benedetti C, Haynes CM, Yang Y, Harding HP, Ron D. Ubiquitin-like protein 5 positively regulates chaperone gene expression in the mitochondrial unfolded protein response. Genetics. 2006;174(1):229-239. doi: 10.1534/genetics.106.061580

 

  1. Jovaisaite V, Mouchiroud L, Auwerx J. The mitochondrial unfolded protein response, a conserved stress response pathway with implications in health and disease. J Exp Biol. 2014;217(1):137-143. doi: 10.1242/jeb.090738

 

  1. Muñoz-Carvajal F, Sanhueza M. The mitochondrial unfolded protein response: A hinge between healthy and pathological aging. Front Aging Neurosci. 2020;12:581849. doi: 10.3389/fnagi.2020.581849

 

  1. Mouchiroud L, Houtkooper RH, Moullan N, et al. The NAD+/sirtuin pathway modulates longevity through activation of mitochondrial UPR and FOXO signaling. Cell. 2013;154(2):430-441. doi: 10.1016/j.cell.2013.06.016

 

  1. Dillin A, Hsu AL, Arantes-Oliveira N, et al. Rates of behavior and aging specified by mitochondrial function during development. Science. 2002;298(5602):2398-2401. doi: 10.3390/nu11092221

 

  1. Durieux J, Wolff S, Dillin A. The cell-non-autonomous nature of electron transport chain-mediated longevity. Cell. 2011;144(1):79-91. doi: 10.1016/j.cell.2010.12.016

 

  1. Han B, Sivaramakrishnan P, Lin CCJ, et al. Microbial genetic composition tunes host longevity. Cell. 2017;169(7):1249- 1262.e13. doi: 10.1016/j.cell.2017.05.036

 

  1. Wu Z, Senchuk MM, Dues DJ, et al. Mitochondrial unfolded protein response transcription factor ATFS-1 promotes longevity in a long-lived mitochondrial mutant through activation of stress response pathways. BMC Biol. 2018;16:147. doi: 10.1186/s12915-018-0615-3

 

  1. Tian Y, Garcia G, Bian Q, et al. Mitochondrial stress induces chromatin reorganization to promote longevity and UPRmt. Cell. 2016;165(5):1197-1208. doi: 10.1016/j.cell.2016.04.011

 

  1. Ono T, Kamimura N, Matsuhashi T, et al. The histone 3 lysine 9 methyltransferase inhibitor chaetocin improves prognosis in a rat model of high salt diet-induced heart failure. Sci Rep. 2017;7(1):39752. doi: 10.1038/srep39752

 

  1. Merkwirth C, Jovaisaite V, Durieux J, et al. Two conserved histone demethylases regulate mitochondrial stress-induced longevity. Cell. 2016;165(5):1209-1223. doi: 10.1016/j.cell.2016.04.012

 

  1. Weng H, Ma Y, Chen L, et al. A new vision of mitochondrial unfolded protein response to the sirtuin family. Curr Neuropharmacol. 2020;18(7):613-623. doi: 10.2174/1570159x18666200123165002

 

  1. Papa L, Germain D. SirT3 regulates the mitochondrial unfolded protein response. Mol Cell Biol. 2014;34(4):699-710. doi: 10.1128/mcb.01337-13

 

  1. Cerutti R, Pirinen E, Lamperti C, et al. NAD+-dependent activation of Sirt1 corrects the phenotype in a mouse model of mitochondrial disease. Cell Metab. 2014;19(6):1042-1049. doi: 10.1016/j.cmet.2014.04.001

 

  1. Cho EH. SIRT3 as a regulator of non-alcoholic fatty liver disease. J Lifestyle Med. 2014;4(2):80-85. doi: 10.15280/jlm.2014.4.2.80

 

  1. Schadel A, Fischer M. Measurement of regional cerebral blood flow and accentuation of the primary auditory cortex with single photon emission computed tomography. Arch Otorhinolaryngol. 1989;246:205-209. doi: 10.1007/bf00453663

 

  1. Chen MM, Li Y, Deng SL, et al. Mitochondrial function and reactive oxygen/nitrogen species in skeletal muscle. Front Cell Dev Biol. 2022;10:826981. doi: 10.3389/fcell.2022.826981

 

  1. Valko M, Leibfritz D, Moncol J, et al. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol. 2007;39(1):44-84. doi: 10.1016/j.biocel.2006.07.001

 

  1. Ott M, Gogvadze V, Orrenius S, Zhivotovsky B. Mitochondria, oxidative stress and cell death. Apoptosis. 2007;12:913-922. doi: 10.1007/s10495-007-0756-2

 

  1. Fogg VC, Lanning NJ, MacKeigan JP. Mitochondria in cancer: At the crossroads of life and death. Chin J Cancer. 2011;30(8):526. doi: 10.5732/cjc.011.10018

 

  1. Milkovic L, Cipak Gasparovic A, Cindric M, Mouthuy PA, Zarkovic N. Short overview of ROS as cell function regulators and their implications in therapy concepts. Cells. 2019;8(8):793. doi: 10.3390/cells8080793

 

  1. Rubio K, Hernández-Cruz EY, Rogel-Ayala DG, et al. Nutriepigenomics in environmental-associated oxidative stress. Antioxidants (Basel). 2023;12(3):771. doi: 10.3390/antiox12030771

 

  1. Agnihotri PK, Murthy PS, Mukherjee SK. Effect of herbicide banvel on rabbit vaginal mucus membrane. Indian J Exp Biol. 1989;27(12):1090-1091.

 

  1. Mills EL, Kelly B, Logan A, et al. Succinate dehydrogenase supports metabolic repurposing of mitochondria to drive inflammatory macrophages. Cell. 2016;167(2):457-470.e13. doi: 10.1016/j.cell.2016.08.064

 

  1. Steinert RF, Grene RB. Postoperative management of epikeratoplasty. J Cataract Refract Surg. 1988;14(3):255-264. doi: 10.1016/s0886-3350(88)80113-5

 

  1. Chouchani ET, Pell VR, James AM, et al. A unifying mechanism for mitochondrial superoxide production during ischemia-reperfusion injury. Cell Metab. 2016;23(2):254-263. doi: 10.1016/j.cmet.2015.12.009

 

  1. Fujimoto Y. Clinical significance of nuclear DNA contents in prostate cancer. Nihon Gan Chiryo Gakkai Shi. 1988;23(6):1265-1276.

 

  1. Poillet-Perez L, Despouy G, Delage-Mourroux R, Boyer- Guittaut M. Interplay between ROS and autophagy in cancer cells, from tumor initiation to cancer therapy. Redox Biol. 2015;4:184-192. doi: 10.1016/j.redox.2014.12.003

 

  1. Powers SK, Ji LL, Kavazis AN, Jackson MJ. Reactive oxygen species: Impact on skeletal muscle. Compr Physiol. 2011;1(2):941. doi: 10.1002/cphy.c100054

 

  1. Venkataraman K, Khurana S, Tai TC. Oxidative stress in aging-matters of the heart and mind. Int J Mol Sci. 2013;14(9):17897-17925. doi: 10.3390/ijms140917897

 

  1. Salisbury D, Bronas U. Reactive oxygen and nitrogen species: Impact on endothelial dysfunction. Nurs Res. 2015;64(1):53-66. doi: 10.1097/nnr.0000000000000068

 

  1. Genestra M. Oxyl radicals, redox-sensitive signalling cascades and antioxidants. Cell Signal. 2007;19(9):1807-1819. doi: 10.1016/j.cellsig.2007.04.009

 

  1. Adams L, Franco MC, Estevez AG. Reactive nitrogen species in cellular signaling. Exp Biol Med. 2015;240(6):711-717. doi: 10.1177/1535370215581314

 

  1. Phaniendra A, Jestadi DB, Periyasamy L. Free radicals: Properties, sources, targets, and their implication in various diseases. Indian J Clin Biochem. 2015;30:11-26. doi: 10.1007/s12291-014-0446-0

 

  1. Frijhoff J, Winyard PG, Zarkovic N, et al. Clinical relevance of biomarkers of oxidative stress. Antioxid Redox Signal. 2015;23(14):1144-1170. doi: 10.1089/ars.2015.6317

 

  1. Birben E, Sahiner UM, Sackesen C, Erzurum S, Kalayci O. Oxidative stress and antioxidant defense. World Allergy Organ J. 2012;5:9-19. doi: 10.1097/wox.0b013e3182439613

 

  1. Wu JQ, Kosten TR, Zhang XY. Free radicals, antioxidant defense systems, and schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2013;46:200-206. doi: 10.1016/j.pnpbp.2013.02.015

 

  1. Pisoschi AM, Pop A. The role of antioxidants in the chemistry of oxidative stress: A review. Eur J Med Chem. 2015;97:55-74. doi: 10.1016/j.ejmech.2015.04.040

 

  1. Lü JM, Lin PH, Yao Q, Chen C. Chemical and molecular mechanisms of antioxidants: Experimental approaches and model systems. J Cell Mol Med. 2010;14(4):840-860. doi: 10.1111/j.1582-4934.2009.00897.x

 

  1. Skrzydlewska E, Augustyniak A, Michalak K, Farbiszewski R. Green tea supplementation in rats of different ages mitigates ethanol-induced changes in brain antioxidant abilities. Alcohol. 2005;37(2):89-98. doi: 10.1016/j.alcohol.2005.12.003

 

  1. Sawada M, Carlson JC. Changes in superoxide radical and lipid peroxide formation in the brain, heart and liver during the lifetime of the rat. Mech Ageing Dev. 1987;41(1-2):125-137. doi: 10.1016/0047-6374(87)90057-1

 

  1. Rao G, Xia E, Richardson A. Effect of age on the expression of antioxidant enzymes in male Fischer F344 rats. Mech Ageing Dev. 1990;53(1):49-60. doi: 10.1016/0047-6374(90)90033-c

 

  1. Murali G, Panneerselvam KS, Panneerselvam C. Age-associated alterations of lipofuscin, membrane-bound ATPases and intracellular calcium in cortex, striatum and hippocampus of rat brain: Protective role of glutathione monoester. Int J Dev Neurosci. 2008;26(2):211-215. doi: 10.1016/j.ijdevneu.2007.12.004

 

  1. Harman D. Free radical theory of aging. Mutat Res. 1992;275(3-6):257-266. doi: 10.1016/0921-8734(92)90030-S

 

  1. Siqueira IR, Fochesatto C, de Andrade A, et al. Total antioxidant capacity is impaired in different structures from aged rat brain. Int J Dev Neurosci. 2005;23(8):663-671. doi: 10.1016/j.ijdevneu.2005.03.001

 

  1. Akila VP, Harishchandra H, D’souza V, D’souza B. Age related changes in lipid peroxidation and antioxidants in elderly people. Indian J Clin Biochem. 2007;22:131-134. doi: 10.1007/bf02912896

 

  1. Rizvi SI, Maurya PK. Alterations in antioxidant enzymes during aging in humans. Mol Biotechnol. 2007;37:58-61. doi: 10.1007/s12033-007-0048-7

 

  1. Wei YH, Lu CY, Lee HC, Pang CY, Ma YS. Oxidative damage and mutation to mitochondrial dna and age‐dependent decline of mitochondrial respiratory function. Ann N Y Acad Sci. 1998;854(1):155-170. doi: 10.1111/j.1749-6632.1998.tb09899.x

 

  1. Ashrafian H, Czibik G, Bellahcene M, et al. Fumarate is cardioprotective via activation of the Nrf2 antioxidant pathway. Cell Metab. 2012;15(3):361-371. doi: 10.1016/j.cmet.2012.01.017

 

  1. Ryan TA, Hooftman A, Rehill AM, et al. Dimethyl fumarate and 4-octyl itaconate are anticoagulants that suppress tissue factor in macrophages via inhibition of type I interferon. Nat Commun. 2023;14(1):3513. doi: 10.1038/s41467-023-39174-1

 

  1. Ellrichmann G, Petrasch-Parwez E, Lee DH, et al. Efficacy of fumaric acid esters in the R6/2 and YAC128 models of Huntington’s disease. PLoS One. 2011;6(1):e16172. doi: 10.1371/journal.pone.0016172

 

  1. Hoyle C, Green JP, Allan SM, Brough D, Lemarchand E. Itaconate and fumarate derivatives inhibit priming and activation of the canonical NLRP3 inflammasome in macrophages. Immunology. 2022;165(4):460-480. doi: 10.1111/imm.13454

 

  1. Sharkus R, Thakkar R, Kolson DL, Constantinescu CS. Dimethyl fumarate as potential treatment for Alzheimer’s disease: Rationale and clinical trial design. Biomedicines. 2023;11(5):1387. doi: 10.3390/biomedicines11051387

 

  1. Scuderi SA, Ardizzone A, Paterniti I, Esposito E, Campolo M. Antioxidant and anti-inflammatory effect of Nrf2 inducer dimethyl fumarate in neurodegenerative diseases. Antioxidants (Basel). 2020;9(7):630. doi: 10.3390/antiox9070630

 

  1. Rosito M, Testi C, Parisi G, Cortese B, Baiocco P, Di Angelantonio S. Exploring the use of dimethyl fumarate as microglia modulator for neurodegenerative diseases treatment. Antioxidants (Basel). 2020;9(8):700. doi: 10.3390/antiox9080700

 

  1. Harrington LA, Harley CB. Effect of vitamin E on lifespan and reproduction in Caenorhabditis elegans. Mech Ageing Dev. 1988;43(1):71-78. doi: 10.1016/0047-6374(88)90098-x

 

  1. Navarro A, Gómez C, Sánchez-Pino MJ, et al. Vitamin E at high doses improves survival, neurological performance, and brain mitochondrial function in aging male mice. Am J Physiol Regul Integr Comp Physiol. 2005;289(5):R1392-R1399. doi: 10.1152/ajpregu.00834.2004

 

  1. Schaffer S, Müller WE, Eckert GP. Tocotrienols: Constitutional effects in aging and disease. J Nutr. 2005;135(2):151-154. doi: 10.1093/jn/135.2.151

 

  1. Collins JJ, Evason K, Kornfeld K. Pharmacology of delayed aging and extended lifespan of Caenorhabditis elegans. Exp Gerontol. 2006;41(10):1032-1039. doi: 10.1016/j.exger.2006.06.038

 

  1. Siler-Marsiglio KI, Pan Q, Paiva M, Madorsky I, Khurana NC, Heaton MB. Mitochondrially targeted vitamin E and vitamin E mitigate ethanol-mediated effects on cerebellar granule cell antioxidant defense systems. Brain Res. 2005;1052(2):202-211. doi: 10.1016/j.brainres.2005.06.030

 

  1. La Fata G, van Vliet N, Barnhoorn S, et al. Vitamin E supplementation reduces cellular loss in the brain of a premature aging mouse model. J Prev Alzheimers Dis. 2017;4(4):226-235. doi: 10.14283/jpad.2017.30

 

  1. Beal MF. Mitochondria, oxidative damage, and inflammation in Parkinson’s disease. Ann N Y Acad Sci. 2003;991(1):120-131. doi: 10.1111/j.1749-6632.2003.tb07470.x

 

  1. Ayunin Q, Miatmoko A, Soeratri W, Erawati T, Susanto J, Legowo D. Improving the anti-ageing activity of coenzyme Q10 through protransfersome-loaded emulgel. Sci Rep. 2022;12(1):906. doi: 10.1038/s41598-021-04708-4

 

  1. Hidalgo-Gutiérrez A, González-García P, Díaz-Casado ME, et al. Metabolic targets of coenzyme Q10 in mitochondria. Antioxidants (Basel). 2021;10(4):520. doi: 10.3390/antiox10040520

 

  1. Acosta MJ, Fonseca LV, Desbats MA, et al. Coenzyme Q biosynthesis in health and disease. Biochim Biophys Acta. 2016;1857(8):1079-1085. doi: 10.1016/j.bbabio.2016.03.036

 

  1. Díaz-Casado ME, Quiles JL, Barriocanal-Casado E, et al. The paradox of coenzyme Q10 in aging. Nutrients. 2019;11(9):2221. doi: 10.3390/nu11092221

 

  1. Muta‐Takada K, Terada T, Yamanishi H, et al. Coenzyme Q10 protects against oxidative stress‐induced cell death and enhances the synthesis of basement membrane components in dermal and epidermal cells. Biofactors. 2009;35(5):435-441. doi: 10.1002/biof.56

 

  1. Inui M, Ooe M, Fujii K, Matsunaka H, Yoshida M, Ichihashi M. Mechanisms of inhibitory effects of CoQ10 on UVB-induced wrinkle formation in vitro and in vivo. Biofactors. 2008;32(1-4):237-243. doi: 10.1002/biof.5520320128

 

  1. Bank G, Kagan D, Madhavi D. Coenzyme Q10: Clinical update and bioavailability. J Evid Based Complement Altern Med. 2011;16(2):129-137. doi: 10.1177/2156587211399438

 

  1. Alcázar-Fabra M, Trevisson E, Brea-Calvo G. Clinical syndromes associated with Coenzyme Q10 deficiency. Essays Biochem. 2018;62(3):377-398. doi: 10.1042/ebc20170107

 

  1. Desbats MA, Lunardi G, Doimo M, Trevisson E, Salviati L. Genetic bases and clinical manifestations of coenzyme Q 10 (CoQ 10) deficiency. J Inherit Metab Dis. 2015;38:145-156. doi: 10.1007/s10545-014-9749-9

 

  1. Quiles JL, Ochoa JJ, Huertas JR, Mataix J. Coenzyme Q supplementation protects from age-related DNA double-strand breaks and increases lifespan in rats fed on a PUFA-rich diet. Exp Gerontol. 2004;39(2):189-194. doi: 10.1016/j.exger.2003.10.002

 

  1. Tomasetti M, Alleva R, Collins AR. In vivo supplementation with coenzyme Q10 enhances the recovery of human lymphocytes from oxidative DNA damage. FASEB J. 2001;15(8):1425-1427. doi: 10.1096/fj.00-0694fje

 

  1. Lönnrot K, Alho H, Holm P, Lagerstedt A, Huhtala H. The effects of lifelong ubiquinone Q10 supplementation on the Q9 and Q10 tissue concentrations and life span of male rats and mice. IUBMB Life. 1998;44(4):727-737. doi: 10.1080/15216549800201772

 

  1. Asencio C, Rodríguez-Aguilera JC, Ruiz-Ferrer M, Vela J, Navas P. Silencing of ubiquinone biosynthesis genes extends life span in Caenorhabditis elegans. FASEB J. 2003;17(9):1135-1137. doi: 10.1096/fj.02-1022fje

 

  1. Larsen PL, Clarke CF. Extension of life-span in Caenorhabditis elegans by a diet lacking coenzyme Q. Science. 2002;295(5552):120-123. doi: 10.1126/science.1064653

 

  1. Zhou D, Shao L, Spitz DR. Reactive oxygen species in normal and tumor stem cells. Adv Cancer Res. 2014;22:1-67. doi: 10.1016/B978-0-12-420117-0.00001-3

 

  1. Chaudhari P, Ye Z, Jang YY. Roles of reactive oxygen species in the fate of stem cells. Antioxid Redox Signal. 2014;20(12):1881-1890. doi: 10.1089/ars.2012.4963

 

  1. Ezashi T, Das P, Roberts RM. Low O2 tensions and the prevention of differentiation of hES cells. Proc Natl Acad Sci. 2005;102(13):4783-4788. doi: 10.1073/pnas.0501283102

 

  1. Shyh-Chang N, Daley GQ, Cantley LC. Stem cell metabolism in tissue development and aging. Development. 2013;140(12):2535-2547. doi: 10.1242/dev.091777

 

  1. Sauer H, Wartenberg M. Reactive oxygen species as signaling molecules in cardiovascular differentiation of embryonic stem cells and tumor-induced angiogenesis. Antioxid Redox Signal. 2005;7(11-12):1423-1434. doi: 10.1089/ars.2005.7.1423

 

  1. Ahlqvist KJ, Hämäläinen RH, Yatsuga S, et al. Somatic progenitor cell vulnerability to mitochondrial DNA mutagenesis underlies progeroid phenotypes in Polg mutator mice. Cell Metab. 2012;15(1):100-109. doi: 10.1016/j.cmet.2011.11.012

 

  1. Chen ML, Logan TD, Hochberg ML, et al. Erythroid dysplasia, megaloblastic anemia, and impaired lymphopoiesis arising from mitochondrial dysfunction. Blood. 2009;114(19):4045-4053. doi: 10.1182/blood-2008-08-169474

 

  1. Hämäläinen RH, Ahlqvist KJ, Ellonen P, et al. mtDNA mutagenesis disrupts pluripotent stem cell function by altering redox signaling. Cell Rep. 2015;11(10):1614-1624. doi: 10.1016/j.celrep.2015.05.009

 

  1. Sun N, Youle RJ, Finkel T. The mitochondrial basis of aging. Mol Cell. 2016;61(5):654-666. doi: 10.1016/j.molcel.2016.01.028

 

  1. Frezza C. Mitochondrial metabolites: Undercover signalling molecules. Interface Focus. 2017;7(2):20160100. doi: 10.1098/rsfs.2016.0100

 

  1. Zhang H, Menzies KJ, Auwerx J. The role of mitochondria in stem cell fate and aging. Development. 2018;145(8):dev143420. doi: 10.1242/dev.143420

 

  1. Carey BW, Finley LW, Cross JR, Allis CD, Thompson CB. Intracellular α-ketoglutarate maintains the pluripotency of embryonic stem cells. Nature. 2015;518(7539):413-416. doi: 10.1038/nature13981

 

  1. McReynolds MR, Chellappa K, Baur JA. Age-related NAD+ decline. Exp Gerontol. 2020;134:110888. doi: 10.1016/j.exger.2020.110888

 

  1. Schultz MB, Sinclair DA. Why NAD+ declines during aging: It’s destroyed. Cell Metab. 2016;23(6):965-966. doi: 10.1016/j.cmet.2016.05.022

 

  1. Cantó C, Sauve AA, Bai P. Crosstalk between poly (ADP-ribose) polymerase and sirtuin enzymes. Mol Aspects Med. 2013;34(6):1168-1201. doi: 10.1016/j.mam.2013.01.004

 

  1. Petriti B, Williams PA, Lascaratos G, Chau KY, Garway- Heath DF. Neuroprotection in glaucoma: NAD+/NADH redox state as a potential biomarker and therapeutic target. Cells 2021;10(6):1402. doi: 10.3390/cells10061402

 

  1. Houtkooper RH, Pirinen E, Auwerx J. Sirtuins as regulators of metabolism and healthspan. Nat Rev Mol Cell Biol. 2012;13(4):225-238. doi: 10.1038/nrm3293

 

  1. Gomes AP, Price NL, Ling AJ, et al. Declining NAD+ induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging. Cell. 2013;155(7):1624-1638. doi: 10.1016/j.cell.2013.11.037

 

  1. Imai S, Guarente L. It takes two to tango: NAD+ and sirtuins in aging/longevity control. NPJ Aging Mech Dis. 2016;2(1):16017. doi: 10.1038/npjamd.2016.17

 

  1. Stein LR, Imai SI. Specific ablation of Nampt in adult neural stem cells recapitulates their functional defects during aging. EMBO J. 2014;33(12):1321-1340. doi: 10.1002/embj.201386917

 

  1. Rajman L, Chwalek K, Sinclair DA. Therapeutic potential of NAD-boosting molecules: The in vivo evidence. Cell Metab. 2018;27(3):529-547. doi: 10.1016/j.cmet.2018.02.011

 

  1. Yoshino J, Mills KF, Yoon MJ, Imai SI. Nicotinamide mononucleotide, a key NAD+ intermediate, treats the pathophysiology of diet-and age-induced diabetes in mice. Cell Metab. 2011;14(4):528-536. doi: 10.1016/j.cmet.2011.08.014

 

  1. Lombard DB, Alt FW, Cheng HL, et al. Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation. Mol Cell Biol. 2007;27(24):8807-8814.doi: 10.1128/mcb.01636-07

 

  1. Brown K, Xie S, Qiu X, et al. SIRT3 reverses aging-associated degeneration. Cell Rep. 2013;3(2):319-327. doi: 10.1016/j.celrep.2013.01.005

 

  1. Shahriyari L, Komarova NL. Symmetric vs. asymmetric stem cell divisions: An adaptation against cancer? PLoS One. 2013;8(10):e76195. doi: 10.1371/journal.pone.0076195

 

  1. Evano B, Khalilian S, Le Carrou G, Almouzni G, Tajbakhsh S. Dynamics of asymmetric and symmetric divisions of muscle stem cells in vivo and on artificial niches. Cell Rep. 2020;30(10):3195-3206.e7. doi: 10.1016/j.celrep.2020.01.097

 

  1. Casas Gimeno G, Paridaen JTML. The symmetry of neural stem cell and progenitor divisions in the vertebrate brain. Front Cell Dev Biol. 2022;10:885269. doi: 10.3389/fcell.2022.885269

 

  1. Yamashita YM, Yuan H, Cheng J, Hunt AJ. Polarity in stem cell division: Asymmetric stem cell division in tissue homeostasis. Cold Spring Harb Perspect Biol. 2010;2(1):a001313. doi: 10.1101/cshperspect.a001313

 

  1. Ito K, Suda T. Metabolic requirements for the maintenance of self-renewing stem cells. Nat Rev Mol Cell Biol. 2014;15(4):243-256. doi: 10.1038/nrm3772

 

  1. Ito K, Carracedo A, Weiss D, et al. A PML–PPAR-δ pathway for fatty acid oxidation regulates hematopoietic stem cell maintenance. Nat Med. 2012;18(9):1350-1358. doi: 10.1038/nm.2882

 

  1. Maffezzini C, Calvo-Garrido J, Wredenberg A, Freyer C. Metabolic regulation of neurodifferentiation in the adult brain. Cell Mol Life Sci. 2020;77:2483-2496. doi: 10.1007/s00018-019-03430-9

 

  1. Angelopoulos I, Gakis G, Birmpas K, et al. Metabolic regulation of the neural stem cell fate: Unraveling new connections, establishing new concepts. Front Neurosci. 2022;16:1009125. doi: 10.3389/fnins.2022.1009125

 

  1. Knobloch M, Braun SM, Zurkirchen L, et al. Metabolic control of adult neural stem cell activity by Fasn-dependent lipogenesis. Nature. 2013;493(7431):226-230. doi: 10.1038/nature11689

 

  1. Ma K, Chen G, Li W, et al. Mitophagy, mitochondrial homeostasis, and cell fate. Front Cell Dev Biol. 2020;8:467. doi: 10.3389/fcell.2020.00467

 

  1. Ding Q, Qi Y, Tsang SY. Mitochondrial biogenesis, mitochondrial dynamics, and mitophagy in the maturation of cardiomyocytes. Cells. 2021;10(9):2463. doi: 10.3390/cells10092463

 

  1. Hall AR, Burke N, Dongworth RK, Hausenloy DJ. Mitochondrial fusion and fission proteins: Novel therapeutic targets for combating cardiovascular disease. Br J Pharmacol. 2014;171(8):1890-1906. doi: 10.1111/bph.12516

 

  1. Adebayo M, Singh S, Singh AP, Dasgupta S. Mitochondrial fusion and fission: The fine-tune balance for cellular homeostasis. FASEB J. 2021;35(6):e21620. doi: 10.1096%2Ffj.202100067R

 

  1. Lemasters JJ. Selective mitochondrial autophagy, or mitophagy, as a targeted defense against oxidative stress, mitochondrial dysfunction, and aging. Rejuvenation Res. 2005;8(1):3-5. doi: 10.1089/rej.2005.8.3

 

  1. Ashrafi G, Schwarz TL. The pathways of mitophagy for quality control and clearance of mitochondria. Cell Death Differ. 2013;20(1):31-42. doi: 10.1038/cdd.2012.81

 

  1. Narendra DP, Jin SM, Tanaka A, et al. PINK1 is selectively stabilized on impaired mitochondria to activate Parkin. PLoS Biol. 2010;8(1):e1000298. doi: 10.1371/journal.pbio.1000298

 

  1. Ma K, Zhang Z, Chang R, et al. Dynamic PGAM5 multimers dephosphorylate BCL-xL or FUNDC1 to regulate mitochondrial and cellular fate. Cell Death Differ. 2020;27(3):1036-1051. doi: 10.1038/s41418-019-0396-4

 

  1. Schapira AH. Mitochondrial pathology in Parkinson’s disease. Mt Sinai J Med. 2011;78(6):872-881. doi: 10.1002/msj.20303

 

  1. Batlevi Y, La Spada AR. Mitochondrial autophagy in neural function, neurodegenerative disease, neuron cell death, and aging. Neurobiol Dis. 2011;43(1):46-51. doi: 10.1016/j.nbd.2010.09.009

 

  1. Lima T, Li TY, Mottis A, Auwerx J. Pleiotropic effects of mitochondria in aging. Nat Aging. 2022;2(3):199-213. doi: 10.1038/s43587-022-00191-2

 

  1. Ryu D, Mouchiroud L, Andreux PA, et al. Urolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents. Nat Med. 2016;22(8):879-888. doi: 10.1038/nm.4132

 

  1. Rera M, Bahadorani S, Cho J, et al. Modulation of longevity and tissue homeostasis by the Drosophila PGC-1 homolog. Cell Metab. 2011;14(5):623-634. doi: 10.1016/j.cmet.2011.09.013

 

  1. Laker RC, Drake JC, Wilson RJ, et al. Ampk phosphorylation of Ulk1 is required for targeting of mitochondria to lysosomes in exercise-induced mitophagy. Nat Commun. 2017;8(1):548. doi: 10.1038/s41467-017-00520-9

 

  1. Kitada T, Asakawa S, Hattori N, et al. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature. 1998;392(6676):605-608. doi: 10.1038/33416

 

  1. Valente EM, Abou-Sleiman PM, Caputo V, et al. Hereditary early-onset Parkinson’s disease caused by mutations in PINK1. Science. 2004;304(5674):1158-1160. doi: 10.1126/science.1096284

 

  1. Wilhelmus MMM, van der Pol SMA, Jansen Q, et al. Association of Parkinson disease-related protein PINK1 with Alzheimer disease and multiple sclerosis brain lesions. Free Radic Biol Med. 2011;50(3):469-476. doi: 10.1016/j.freeradbiomed.2010.11.033

 

  1. Witte ME, Bol JG, Gerritsen WH, et al. Parkinson’s disease-associated parkin colocalizes with Alzheimer’s disease and multiple sclerosis brain lesions. Neurobiol Dis. 2009;36(3):445-452. doi: 10.1016/j.nbd.2009.08.009

 

  1. Cummins N, Tweedie A, Zuryn S, Bertran‐Gonzalez J, Götz J. Disease‐associated tau impairs mitophagy by inhibiting Parkin translocation to mitochondria. EMBO J. 2019;38(3):e99360. doi: 10.15252/embj.201899360

 

  1. Ryan TA, Tumbarello DA. A central role for mitochondrial-derived vesicles in the innate immune response: Implications for Parkinson’s disease. Neural Regeneration Res. 2021;16(9):1779. doi: 10.4103/1673-5374.306074

 

  1. Twig G, Hyde B, Shirihai OS. Mitochondrial fusion, fission and autophagy as a quality control axis: The bioenergetic view. Biochim Biophys Acta. 2008;1777(9):1092-1097. doi: 10.1016/j.bbabio.2008.05.001

 

  1. Chistiakov DA, Sobenin IA, Revin VV, Orekhov AN, Bobryshev YV. Mitochondrial aging and age-related dysfunction of mitochondria. Biomed Res Int. 2014;2014:238463. doi: 10.1155/2014/238463

 

  1. Nakahira K, Hisata S, Choi AMK. The roles of mitochondrial damage-associated molecular patterns in diseases. Antioxid Redox Signal. 2015;23(17):1329-1350. doi: 10.1089/ars.2015.6407

 

  1. Luna-Sánchez M, Bianchi P, Quintana A. Mitochondria-induced immune response as a trigger for neurodegeneration: A pathogen from within. Int J Mol Sci. 2021;22(16):8523. doi: 10.3390/ijms22168523

 

  1. Zhang Q, Raoof M, Chen Y, et al. Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature. 2010;464(7285):104-107. doi: 10.1038/nature08780

 

  1. Collins LV, Hajizadeh S, Holme E, Jonsson IM, Tarkowski A. Endogenously oxidized mitochondrial DNA induces in vivo and in vitro inflammatory responses. J Leukoc Biol. 2004;75(6):995-1000. doi: 10.1189/jlb.0703328

 

  1. Wu J, Sun L, Chen X, et al. Cyclic GMP-AMP is an endogenous second messenger in innate immune signaling by cytosolic DNA. Science. 2013;339(6121):826-830. doi: 10.1126/science.1229963

 

  1. Oka T, Hikoso S, Yamaguchi O, et al. Mitochondrial DNA that escapes from autophagy causes inflammation and heart failure. Nature. 2012;485(7397):251-255. doi: 10.1038/nature10992

 

  1. Shimada K, Crother TR, Karlin J, et al. Oxidized mitochondrial DNA activates the NLRP3 inflammasome during apoptosis. Immunity. 2012;36(3):401-414. doi: 10.1016/j.immuni.2012.01.009

 

  1. Youm YH, Grant RW, McCabe LR, et al. Canonical Nlrp3 inflammasome links systemic low-grade inflammation to functional decline in aging. Cell Metab. 2013;18(4):519-532. doi: 10.1016/j.cmet.2013.09.010

 

  1. Pinti M, Cevenini E, Nasi M, et al. Circulating mitochondrial DNA increases with age and is a familiar trait: Implications for “inflamm‐aging”. Eur J Immunol. 2014;44(5):1552-1562. doi: 10.1002/eji.201343921

 

  1. Trumpff C, Michelson J, Lagranha CJ, et al. Stress and circulating cell-free mitochondrial DNA: A systematic review of human studies, physiological considerations, and technical recommendations. Mitochondrion. 2021;59:225-245. doi: 10.1016/j.mito.2021.04.002

 

  1. Logan DC. The mitochondrial compartment. J Exp Bot. 2006;57(6):1225-1243. doi: 10.1093/jxb/erj151

 

  1. Buchke S, Sharma M, Bora A, Relekar M, Bhanu P, Kumar JJL. Mitochondria-targeted, nanoparticle-based drug-delivery systems: Therapeutics for mitochondrial disorders. Life (Basel). 2022;12(5):657. doi: 10.3390/life12050657

 

  1. Sarvari P, Sarvari P. Advances in nanoparticle-based drug delivery in cancer treatment. Glob Transl Med. 2023;2(2):0394. doi: 10.36922/gtm.0394

 

  1. Sarvari P, Sarvari P, Ramírez-Díaz I, Mahjoubi F, Rubio K. Advances of epigenetic biomarkers and epigenome editing for early diagnosis in breast cancer. Int J Mol Sci. 2022;23(17):9521. doi: 10.3390/ijms23179521

 

  1. Kalyane D, Raval N, Maheshwari R, Tambe V, Kalia K, Tekade RK. Employment of enhanced permeability and retention effect (EPR): Nanoparticle-based precision tools for targeting of therapeutic and diagnostic agent in cancer. Mater Sci Eng C Mater Biol Appl. 2019;98:1252-1276. doi: 10.1016/j.msec.2019.01.066

 

  1. Zhang L, Chan JM, Gu FX, et al. Self-assembled lipid polymer hybrid nanoparticles: A robust drug delivery platform. ACS Nano. 2008;2(8):1696-1702. doi: 10.1021/nn800275r

 

  1. Porporato PE, Filigheddu N, Pedro JMBS, Kroemer G, Galluzzi L. Mitochondrial metabolism and cancer. Cell Res. 2018;28(3):265-280. doi: 10.1038/cr.2017.155

 

  1. Pandey S, Nandi A, Basu S, Ballav N. Inducing endoplasmic reticulum stress in cancer cells using graphene oxide-based nanoparticles. Nanoscale Adv. 2020;2(10):4887-4894. doi: 10.1039/d0na00338g

 

  1. Bonam SR, Wang F, Muller S. Lysosomes as a therapeutic target. Nat Rev Drug Discov. 2019;18(12):923-948. doi: 10.1038/s41573-019-0036-1

 

  1. Tabish TA, Hamblin MR. Mitochondria-targeted nanoparticles (mitoNANO): An emerging therapeutic shortcut for cancer. Biomater Biosyst. 2021;3:100023. doi: 10.1016/s0005-2728(98)00161-3

 

  1. Huang Y, Sun G, Sun X, et al. The potential of lonidamine in combination with chemotherapy and physical therapy in cancer treatment. Cancers (Basel). 2020;12(11):3332. doi: 10.3390/cancers12113332

 

  1. Yang SK, Han YC, He JR, et al. Mitochondria targeted peptide SS-31 prevent on cisplatin-induced acute kidney injury via regulating mitochondrial ROS-NLRP3 pathway. Biomed Pharmacother. 2020;130:110521. doi: 10.1016/j.biopha.2020.110521

 

  1. Cheng G, Zhang Q, Pan J, et al. Targeting lonidamine to mitochondria mitigates lung tumorigenesis and brain metastasis. Nat Commun. 2019;10(1):2205. doi: 10.1038/s41467-019-10042-1

 

  1. Cheng G, Zielonka J, Dranka BP, et al. Mitochondria-targeted drugs synergize with 2-deoxyglucose to trigger breast cancer cell death. Cancer Res. 2012;72(10):2634-2644. doi: 10.1158/0008-5472.can-11-3928

 

  1. Zhang D, Wen L, Huang R, Wang H, Hu X, Xing D. Mitochondrial specific photodynamic therapy by rare-earth nanoparticles mediated near-infrared graphene quantum dots. Biomaterials. 2018;153:14-26. doi: 10.1016/j.biomaterials.2017.10.034

 

  1. Cheng X, Feng D, Lv J, et al. Application prospects of triphenylphosphine-based mitochondria-targeted cancer therapy. Cancers (Basel). 2023;15(3):666. doi: 10.3390/cancers15030666

 

  1. Dong L, Gopalan V, Holland O, Neuzil J. Mitocans revisited: Mitochondrial targeting as efficient anti-cancer therapy. Int J Mol Sci. 2020;21(21):7941. doi: 10.3390/ijms21217941

 

  1. Cheng G, Zielonka J, McAllister DM, et al. Mitochondria-targeted vitamin E analogs inhibit breast cancer cell energy metabolism and promote cell death. BMC Cancer. 2013;13(1):285. doi: 10.1186/1471-2407-13-285

 

  1. Battogtokh G, Choi YS, Kang DS, et al. Mitochondria-targeting drug conjugates for cytotoxic, anti-oxidizing and sensing purposes: Current strategies and future perspectives. Acta Pharm Sin B. 2018;8(6):862-880. doi: 10.1016/j.apsb.2018.05.006

 

  1. Iacopetta D, Ceramella J, Rosano C, et al. N-Heterocyclic carbene-gold (I) complexes targeting actin polymerization. Appl Sci. 2021;11(12):5626. doi: 10.3390/app11125626

 

  1. Odyniec ML, Han HH, Gardiner JE, et al. Peroxynitrite activated drug conjugate systems based on a coumarin scaffold toward the application of theranostics. Front Chem. 2019;7:775. doi: 10.3389/fchem.2019.00775

 

  1. Cheng G, Zielonka J, Ouari O, et al. Mitochondria-targeted analogues of metformin exhibit enhanced antiproliferative and radiosensitizing effects in pancreatic cancer cells. Cancer Res. 2016;76(13):3904-3915. doi: 10.1158/0008-5472.can-15-2534

 

  1. Smith RA, Porteous CM, Gane AM, Murphy MP. Delivery of bioactive molecules to mitochondria in vivo. Proc Natl Acad Sci U S A. 2003;100(9):5407-5412. doi: 10.1073/pnas.0931245100

 

  1. Zielonka J, Joseph J, Sikora A, et al. Mitochondria-targeted triphenylphosphonium-based compounds: Syntheses, mechanisms of action, and therapeutic and diagnostic applications. Chem Rev. 2017;117(15):10043-10120. doi: 10.1021/acs.chemrev.7b00042

 

  1. Agrawal M, Saraf S, Pradhan M, et al. Design and optimization of curcumin loaded nano lipid carrier system using Box- Behnken design. Biomed Pharmacother. 2021;141:111919. doi: 10.1016/j.biopha.2021.111919

 

  1. Fonseca-Santos B, Gremião MPD, Chorilli M. Nanotechnology-based drug delivery systems for the treatment of Alzheimer’s disease. Int J Nanomedicine. 2015;10:4981-5003. doi: 10.2147/ijn.s87148

 

  1. Masserini M. Nanoparticles for brain drug delivery. ISRN Biochem. 2013;2013:238428. doi: 10.1155/2013/238428

 

  1. Yang X, Li J, Chen H, et al. Uptake of silica nanoparticles: Neurotoxicity and Alzheimer-like pathology in human SK-N-SH and mouse neuro2a neuroblastoma cells. Toxicol Lett. 2014;229(1):240-249. doi: 10.1016/j.toxlet.2014.05.009

 

  1. Sharma A, Liaw K, Sharma R, Zhang Z, Kannan S, Kannan RM. Targeting mitochondrial dysfunction and oxidative stress in activated microglia using dendrimer-based therapeutics. Theranostics. 2018;8(20):5529-5547. doi: 10.7150/thno.29039

 

  1. Gaj T, Gersbach CA, Barbas CF 3rd. ZFN, TALEN, and CRISPR/Cas-based methods for genome engineering. Trends Biotechnol. 2013;31(7):397-405. doi: 10.1016/j.tibtech.2013.04.004

 

  1. Juan T, Ribeiro da Silva A, Cardoso B, Lim S, Charteau V, Stainier DYR. Multiple pkd and piezo gene family members are required for atrioventricular valve formation. Nat Commun. 2023;14(1):214. doi: 10.1038/s41467-023-35843-3

 

  1. Deng HX, Zhai H, Shi Y, et al. Efficacy and long-term safety of CRISPR/Cas9 genome editing in the SOD1-linked mouse models of ALS. Commun Biol. 2021;4(1):396. doi: 10.1038/s42003-021-01942-4

 

  1. Sarvari P, Rasouli SJ, Allanki S, et al. The E3 ubiquitin-protein ligase Rbx1 regulates cardiac wall morphogenesis in zebrafish. Dev Biol. 2021;480:1-12. doi: 10.1016/j.ydbio.2021.07.019

 

  1. Wang H, Hu YC, Markoulaki S, et al. TALEN-mediated editing of the mouse Y chromosome. Nat Biotechnol. 2013;31(6):530-532. doi: 10.1038/nbt.2595

 

  1. Carlson DF, Tan W, Lillico SG, et al. Efficient TALEN-mediated gene knockout in livestock. Proc Natl Acad Sci U S A. 2012;109(43):17382-17387. doi: 10.1073/pnas.1211446109

 

  1. Phan HTL, Lee H, Kim K. Trends and prospects in mitochondrial genome editing. Exp Mol Med. 2023;55:871-878. doi: 10.1038/s12276-023-00973-7

 

  1. Srivastava S, Moraes CT. Manipulating mitochondrial DNA heteroplasmy by a mitochondrially targeted restriction endonuclease. Hum Mol Genet. 2001;10(26):3093-3099. doi: 10.1093/hmg/10.26.3093

 

  1. Tanaka M, Borgeld HJ, Zhang J, et al. Gene therapy for mitochondrial disease by delivering restriction endonuclease SmaI into mitochondria. J Biomed Sci. 2002;9(6):534-541. doi: 10.1159/000064726

 

  1. Bayona-Bafaluy MP, Blits B, Battersby BJ, Shoubridge EA, Moraes CT. Rapid directional shift of mitochondrial DNA heteroplasmy in animal tissues by a mitochondrially targeted restriction endonuclease. Proc Natl Acad Sci U S A. 2005;102(40):14392-14397. doi: 10.1073/pnas.0502896102

 

  1. Reddy P, Ocampo A, Suzuki K, et al. Selective elimination of mitochondrial mutations in the germline by genome editing. Cell. 2015;161(3):459-469. doi: 10.1016/j.cell.2015.03.051

 

  1. Minczuk M, Papworth MA, Miller JC, Murphy MP, Klug A. Development of a single-chain, quasi-dimeric zinc-finger nuclease for the selective degradation of mutated human mitochondrial DNA. Nucleic Acids Res. 2008;36(12):3926-3938. doi: 10.1093/nar/gkn313

 

  1. Bacman SR, Williams SL, Pinto M, Peralta S, Moraes CT. Specific elimination of mutant mitochondrial genomes in patient-derived cells by mitoTALENs. Nat Med. 2013;19(9):1111-1113. doi: 10.1038/nm.3261

 

  1. Gammage PA, Rorbach J, Vincent AI, Rebar EJ, Minczuk M. Mitochondrially targeted ZFN s for selective degradation of pathogenic mitochondrial genomes bearing large‐scale deletions or point mutations. EMBO Mol Med. 2014;6(4):458-466. doi: 10.1002/emmm.201303672

 

  1. Gammage PA, Gaude E, Van Haute L, et al. Near-complete elimination of mutant mtDNA by iterative or dynamic dose-controlled treatment with mtZFNs. Nucleic Acids Res. 2016;44(16):7804-7816. doi: 10.1093/nar/gkw676

 

  1. Bacman SR, Kauppila JH, Pereira CV, et al. MitoTALEN reduces mutant mtDNA load and restores tRNAAla levels in a mouse model of heteroplasmic mtDNA mutation. Nat Med. 2018;24(11):1696-1700. doi: 10.1038/s41591-018-0166-8

 

  1. Gammage PA, Viscomi C, Simard ML, et al. Genome editing in mitochondria corrects a pathogenic mtDNA mutation in vivo. Nat Med. 2018;24(11):1691-1695. doi: 10.1038/s41591-018-0165-9

 

  1. Yin T, Luo J, Huang D, Li H. Current progress of mitochondrial genome editing by CRISPR. Front Physiol. 2022;13:883459. doi: 10.3389/fphys.2022.883459

 

  1. Pereira CV, Bacman SR, Arguello T, et al. mitoTev‐ TALE: A monomeric DNA editing enzyme to reduce mutant mitochondrial DNA levels. EMBO Mol Med. 2018;10(9):e8084. doi: 10.15252/emmm.201708084

 

  1. Mok BY, de Moraes MH, Zeng J, et al. A bacterial cytidine deaminase toxin enables CRISPR-free mitochondrial base editing. Nature. 2020;583(7817):631-637. doi: 10.1038/s41586-020-2477-4

 

  1. Lee H, Lee S, Baek G, et al. Mitochondrial DNA editing in mice with DddA-TALE fusion deaminases. Nat Commun. 2021;12(1):1190. doi: 10.1038/s41467-021-21464-1

 

  1. Silva-Pinheiro P, Minczuk M. The potential of mitochondrial genome engineering. Nat Rev Genet. 2022;23(4):199-214. doi: 10.1038/s41576-021-00432-x

 

  1. Silva-Pinheiro P, Nash PA, Van Haute L, Mutti CD, Turner K, Minczuk M. In vivo mitochondrial base editing via adeno-associated viral delivery to mouse post-mitotic tissue. Nat Commun. 2022;13(1):750. doi: 10.1038/s41467-022-28358-w

 

  1. Wei Y, Xu C, Feng H, et al. Human cleaving embryos enable efficient mitochondrial base-editing with DdCBE. Cell Discov. 2022;8(1):7. doi: 10.1038/s41421-021-00372-0

 

  1. Sabharwal A, Kar B, Restrepo-Castillo S, et al. The FusX TALE Base Editor (FusXTBE) for rapid mitochondrial DNA programming of human cells in vitro and zebrafish disease models in vivo. CRISPR J. 2021;4(6):799-821. doi: 10.1089/crispr.2021.0061

 

  1. Guo J, Zhang X, Chen X, et al. Precision modeling of mitochondrial diseases in zebrafish via DdCBE-mediated mtDNA base editing. Cell Discov. 2021;7(1):78. doi: 10.1038/s41421-021-00307-9

 

  1. Guo J, Chen X, Liu Z, et al. DdCBE mediates efficient and inheritable modifications in mouse mitochondrial genome. Mol Ther Nucleic Acids. 2022;27:73-80. doi: 10.1016/j.omtn.2021.11.016

 

  1. Qi X, Chen X, Guo J, et al. Precision modeling of mitochondrial disease in rats via DdCBE-mediated mtDNA editing. Cell Discov. 2021;7(1):95. doi: 10.1038/s41421-021-00325-7

 

  1. Nakazato I, Okuno M, Yamamoto H, et al. Targeted base editing in the plastid genome of Arabidopsis thaliana. Nat Plants. 2021;7(7):906-913. doi: 10.1038/s41477-021-00954-6

 

  1. Moraes CT. A magic bullet to specifically eliminate mutated mitochondrial genomes from patients’ cells. EMBO Mol Med. 2014;6(4):434-435. doi: 10.1002/emmm.201303769

 

  1. Hsu PD, Scott DA, Weinstein JA, et al. DNA targeting specificity of RNA-guided Cas9 nucleases. Nat Biotechnol. 2013;31(9):827-832. doi: 10.1038/nbt.2647

 

  1. Ran FA, Hsu PD, Wright J, Agarwala V, Scott DA, Zhang F. Genome engineering using the CRISPR-Cas9 system. Cell Metab. 2013;8(11):2281-2308. doi: 10.1016/j.cmet.2018.02.011

 

  1. Doudna JA, Charpentier E. The new frontier of genome engineering with CRISPR-Cas9. Science. 2014;346(6213):1258096. doi: 10.1126/science.1258096

 

  1. Jo A, Ham S, Lee GH, et al. Efficient mitochondrial genome editing by CRISPR/Cas9. Biomed Res Int. 2015;2015:305716. doi: 10.1155/2015/305716

 

  1. Bian WP, Chen YL, Luo JJ, Wang C, Xie SL, Pei DS. Knock-in strategy for editing human and zebrafish mitochondrial DNA using mito-CRISPR/Cas9 system. ACS Synth Biol. 2019;8(4):621-632. doi: 10.1021/acssynbio.8b00411

 

  1. Hussain SRA, Yalvac ME, Khoo B, Eckardt S, McLaughlin KJ. Adapting CRISPR/Cas9 system for targeting mitochondrial genome. Front Genet. 2021;12:627050. doi: 10.3389/fgene.2021.627050

 

  1. Kauppila TE, Kauppila JH, Larsson NG. Mammalian mitochondria and aging: An update. Cell Metab. 2017;25(1):57-71. doi: 10.1016/j.cmet.2016.09.017

 

  1. Hirose M, Schilf P, Gupta Y, et al. Low-level mitochondrial heteroplasmy modulates DNA replication, glucose metabolism and lifespan in mice. Sci Rep. 2018;8(1):5872. doi: 10.1038/s41598-018-24290-6
Conflict of interest
The authors declare they have no competing interests.
Share
Back to top
INNOSC Theranostics and Pharmacological Sciences, Electronic ISSN: 2705-0823 Published by AccScience Publishing