Reduced cardiolipin content decreases respiratory chain capacities and increases ATP synthesis yield in the human HepaRG cells

Biochimica Et Biophysica Acta
Laure PeytaStéphane Servais

Abstract

Cardiolipin (CL) is a unique mitochondrial phospholipid potentially affecting many aspects of mitochondrial function/processes, i.e. energy production through oxidative phosphorylation. Most data focusing on implication of CL content and mitochondrial bioenergetics were performed in yeast or in cellular models of Barth syndrome. Previous work reported that increase in CL content leads to decrease in liver mitochondrial ATP synthesis yield. Therefore the aim of this study was to determine the effects of moderate decrease in CL content on mitochondrial bioenergetics in human hepatocytes. For this purpose, we generated a cardiolipin synthase knockdown (shCLS) in HepaRG hepatoma cells showing bioenergetics features similar to primary human hepatocytes. shCLS cells exhibited a 55% reduction in CLS gene and a 40% decrease in protein expression resulting in a 45% lower content in CL compared to control (shCTL) cells. Oxygen consumption was significantly reduced in shCLS cells compared to shCTL regardless of substrate used and energy state analyzed. Mitochondrial low molecular weight supercomplex content was higher in shCLS cells (+60%) compared to shCTL. Significant fragmentation of the mitochondrial network was observed in shCLS cell...Continue Reading

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Citations

Mar 7, 2017·Scientific Reports·Estefanía Acaz-FonsecaMariana Astiz
Mar 3, 2017·Nutrition & Metabolism·Thomas N SeyfriedDominic P D'Agostino
Apr 20, 2018·The Journal of Pharmacology and Experimental Therapeutics·Dounia Le GuillouBernard Fromenty
Sep 20, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·David SchädeliPeter Bütikofer
Jan 1, 2017·Cellular and Molecular Neurobiology·Caitlin B Pointer, Andis Klegeris
Feb 29, 2020·Scientific Reports·Katherine PhanWoojin Scott Kim
Mar 29, 2018·Journal of Bioenergetics and Biomembranes·Béatrice ChabiChristine Feillet-Coudray
Sep 11, 2019·Scientific Reports·Adeline PivertAlexandra Ducancelle
May 20, 2020·International Journal of Molecular Sciences·Juliette LeglerJorke H Kamstra
Aug 30, 2018·Lipids in Health and Disease·Wan-Hsin ChangYuan-Hao Howard Hsu
Nov 9, 2021·Molecular Metabolism·Tomás DurajAngel Ayuso-Sacido
Sep 16, 2020·Biochimica Et Biophysica Acta. Biomembranes·Shani Ben ZichriRaz Jelinek

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