Dysfunctional oxidative phosphorylation shunts branched-chain amino acid catabolism onto lipogenesis in skeletal muscle.

ABSTRACT: It is controversial whether mitochondrial dysfunction in skeletal muscle is the cause or consequence of metabolic disorders. Herein, we demonstrate that in vivo inhibition of mitochondrial ATP synthase in muscle alters whole-body lipid homeostasis. Mice with restrained mitochondrial ATP synthase activity presented intrafiber lipid droplets, dysregulation of acyl-glycerides, and higher visceral adipose tissue deposits, poising these animals to insulin resistance. This mitochondrial energy crisis increases lactate production, prevents fatty acid β-oxidation, and forces the catabolism of branched-chain amino acids (BCAA) to provide acetyl-CoA for de novo lipid synthesis. In turn, muscle accumulation of acetyl-CoA leads to acetylation-dependent inhibition of mitochondrial respiratory complex I

SUBMITTER: Sanchez-Gonzalez C 

PROVIDER: S-EPMC7360968 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature