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Cardiolipin content controls mitochondrial coupling and energetic efficiency in muscle

Abstract : Unbalanced energy partitioning participates in the rise of obesity, a major public health concern in many countries. Increasing basal energy expenditure has been proposed as a strategy to fight obesity yet raises efficiency and safety concerns. Here, we show that mice deficient for a muscle-specific enzyme of very-long-chain fatty acid synthesis display increased basal energy expenditure and protection against high-fat diet–induced obesity. Mechanistically, muscle-specific modulation of the very-long-chain fatty acid pathway was associated with a reduced content of the inner mitochondrial membrane phospholipid cardiolipin and a blunted coupling efficiency between the respiratory chain and adenosine 5′-triphosphate (ATP) synthase, which was restored by cardiolipin enrichment. Our study reveals that selective increase of lipid oxidative capacities in skeletal muscle, through the cardiolipin-dependent lowering of mitochondrial ATP production, provides an effective option against obesity at the whole-body level.
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Alexandre Prola, Jordan Blondelle, Aymeline Vandestienne, Jérôme Piquereau, Raphaël Denis, et al.. Cardiolipin content controls mitochondrial coupling and energetic efficiency in muscle. Science Advances , American Association for the Advancement of Science (AAAS), 2021, 7 (1), pp.eabd6322. ⟨10.1126/sciadv.abd6322⟩. ⟨hal-03105418⟩

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