AccScience Publishing / EJMO / Online First / DOI: 10.36922/EJMO026260303
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Yuki Tabata
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ORIGINAL RESEARCH ARTICLE

Phospholipid distribution of endogenous geranylgeranoic acid and its zaragozic acid A–induced shift toward cardiolipin-enriched fractions

Yuki Tabata1*
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1 Department of Nursing, Faculty of Nursing, Miyazaki Prefectural Nursing University, Miyazaki, Miyazaki Prefecture , Japan
EJMO, 026260303 https://doi.org/10.36922/EJMO026260303
Received: 24 June 2026 | Revised: 27 July 2026 | Accepted: 24 August 2026 | Published online: 28 August 2026
© 2026 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 the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

Introduction: Geranylgeranoic acid (GGA) is an endogenous lipid mediator implicated in hepatocellular carcinogenesis, but its phospholipid-associated intracellular distribution remains poorly defined.

Objectives: To characterize the lipid-fraction distribution of endogenous GGA in HuH-7 hepatoma cells and determine whether enhanced non-sterol isoprenoid flux alters its recovery from phospholipid-associated fractions.

Methods: HuH-7 cells were analyzed under basal conditions and after treatment with squalestatin-1/zaragozic acid A (ZAA), a squalene synthase inhibitor. Cellular lipids were separated by thin-layer chromatography (TLC), followed by alkaline hydrolysis and GGA quantification using liquid chromatography-tandem mass spectrometry. Polar lipids were further separated to assess recovery from phosphatidylcholine (PC), phosphatidylethanolamine (PE), and solvent-front/cardiolipin (CL)-enriched fractions. Supplementary CL-resolving TLC was also performed.

Results: Under basal conditions, GGA was recovered mainly from polar lipids, predominantly in PC and, to a lesser extent, PE fractions, whereas the solvent-front/CL-enriched fraction contained only minor amounts. ZAA increased GGA recovery 6.0-fold from the free fatty acid fraction and 2.2-fold from the polar lipid fraction. Within phospholipid-containing fractions, ZAA increased recovery 18.2-fold from the solvent-front/CL-enriched fraction, while PC remained relatively unchanged and PE decreased modestly. Supplementary CL-resolving analysis supported recovery from a CL-associated fraction.

Conclusion: GGA was recovered after alkaline hydrolysis of TLC fractions; however, this does not establish covalent esterification or identify the relevant intact molecular species. Increased intracellular GGA availability was accompanied by expansion of a CL-associated recoverable pool, supporting future investigation of its relationship to mitochondrial lipid remodeling and hepatoma-cell stress responses.

Keywords
Geranylgeranoic acid
Cardiolipin
Phosphatidylcholine
Phosphatidylethanolamine
Zaragozic acid A
LC-MS/MS
Funding
This work was supported by JSPS KAKENHI Grant Numbers JP23K16802 and JP26K21093.
Conflict of interest
The author declares no conflicts of interest.
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Eurasian Journal of Medicine and Oncology, Electronic ISSN: 2587-196X Print ISSN: 2587-2400, Published by AccScience Publishing
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