article · 01/01/2021
Cardiolipin content controls mitochondrial coupling and energetic efficiency in muscle
Résumé
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.
Citer cet article
Prola, A., Blondelle, J., Vandestienne, A., Piquereau, J., Denis, R., Guyot, S., Chauvin, H., Mourier, A., Maurer, M., Henry, C., Khadhraoui, N., Gallerne, C., Molinié, T., Courtin, G., Guillaud, L., Gressette, M., Solgadi, A., Dumont, F., Castel, J., Ternacle, J., Demarquoy, J., Malgoyre, A., Koulmann, N., Derumeaux, G., Giraud, M.-F., Joubert, F., Veksler, V., Luquet, S., Relaix, F., Tiret, L., & Pilot-Storck, F. (2021). Cardiolipin content controls mitochondrial coupling and energetic efficiency in muscle. Science Advances, 7(1), eabd6322. https://doi.org/https://doi.org/10.1126/sciadv.abd6322@article{Prola2021_332,
author = {Prola, Alexandre and Blondelle, Jordan and Vandestienne, Aymeline and Piquereau, Jérôme and Denis, Raphaël and Guyot, Stéphane and Chauvin, Hadrien and Mourier, Arnaud and Maurer, Marie and Henry, Céline and Khadhraoui, Nahed and Gallerne, Cindy and Molinié, Thibaut and Courtin, Guillaume and Guillaud, Laurent and Gressette, Mélanie and Solgadi, Audrey and Dumont, Florent and Castel, Julien and Ternacle, Julien and Demarquoy, Jean and Malgoyre, Alexandra and Koulmann, Nathalie and Derumeaux, Geneviève and Giraud, Marie-France and Joubert, Frédéric and Veksler, Vladimir and Luquet, Serge and Relaix, Frédéric and Tiret, Laurent and Pilot-Storck, Fanny},
year = {2021},
month = {1},
title = {Cardiolipin content controls mitochondrial coupling and energetic efficiency in muscle},
journal = {Science Advances},
volume = {7},
number = {1},
pages = {eabd6322},
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.},
doi = {https://doi.org/10.1126/sciadv.abd6322},
}TY - JOUR
AU - Prola, Alexandre
AU - Blondelle, Jordan
AU - Vandestienne, Aymeline
AU - Piquereau, Jérôme
AU - Denis, Raphaël
AU - Guyot, Stéphane
AU - Chauvin, Hadrien
AU - Mourier, Arnaud
AU - Maurer, Marie
AU - Henry, Céline
AU - Khadhraoui, Nahed
AU - Gallerne, Cindy
AU - Molinié, Thibaut
AU - Courtin, Guillaume
AU - Guillaud, Laurent
AU - Gressette, Mélanie
AU - Solgadi, Audrey
AU - Dumont, Florent
AU - Castel, Julien
AU - Ternacle, Julien
AU - Demarquoy, Jean
AU - Malgoyre, Alexandra
AU - Koulmann, Nathalie
AU - Derumeaux, Geneviève
AU - Giraud, Marie-France
AU - Joubert, Frédéric
AU - Veksler, Vladimir
AU - Luquet, Serge
AU - Relaix, Frédéric
AU - Tiret, Laurent
AU - Pilot-Storck, Fanny
PY - 2021
DA - 2021/01/01
TI - Cardiolipin content controls mitochondrial coupling and energetic efficiency in muscle
JO - Science Advances
VL - 7
IS - 1
AB - 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.
SP - eabd6322
DO - https://doi.org/10.1126/sciadv.abd6322
ER -