Peyta 2016 Biochim Biophys Acta

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Peyta L, Jarnouen K, Pinault M, Guimaraes C, Pais de Barros JP, Chevalier S, Dumas JF, Maillot F, Hatch GM, Loyer P, Servais S (2016) Reduced cardiolipin content decreases respiratory chain capacities and increases ATP synthesis yield in the human HepaRG cells. Biochim Biophys Acta 1857:443-53.

» PMID: 26768115

Peyta L, Jarnouen K, Pinault M, Guimaraes C, Pais de Barros JP, Chevalier S, Dumas JF, Maillot F, Hatch GM, Loyer P, Servais S (2016) Biochim Biophys Acta

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 cells compared to shCTL cells. Surprisingly, mitochondrial ATP synthesis was unchanged in shCLS compared to shCTL cells but exhibited a higher ATP:O ratio (+46%) in shCLS cells. Our results suggest that lowered respiratory chain activity induced by moderate reduction in CL content may be due to both destabilization of supercomplexes and mitochondrial network fragmentation. In addition, CL content may regulate mitochondrial ATP synthesis yield.

Copyright © 2016 Elsevier B.V. All rights reserved.

Keywords: Cardiolipin synthase, Hepatocytes, Mitochondrial network, Oxidative phosphorylation, Supercomplexes, Human HepaRG cells, HuH-7 liver carcinoma cells, Human primary hepatocytes

O2k-Network Lab: FR Tours Dumas JF

Labels: MiParea: Respiration, Genetic knockout;overexpression 

Organism: Human  Tissue;cell: Liver, Other cell lines  Preparation: Permeabilized cells  Enzyme: Supercomplex  Regulation: Fatty acid  Coupling state: LEAK, OXPHOS, ET  Pathway: N, CIV, NS, ROX  HRR: Oxygraph-2k