Loss of mitochondrial calcium uniporter rewires skeletal muscle metabolism and substrate preference.

ABSTRACT: Skeletal muscle mitochondria readily accumulate Ca²⁺ in response to SR store-releasing stimuli thanks to the activity of the mitochondrial calcium uniporter (MCU), the highly selective channel responsible for mitochondrial Ca²⁺ uptake. MCU positively regulates myofiber size in physiological conditions and counteracts pathological loss of muscle mass. Here we show that skeletal muscle-specific MCU deletion inhibits myofiber mitochondrial Ca²⁺ uptake, impairs muscle force and exercise performance, and determines a slow to fast switch in MHC expression. Mitochondrial Ca²⁺ uptake is required for effective glucose oxidation, as demonstrated by the fact that in muscle-specific MCU^-/- myofibers oxidative metabolism is impaired and

SUBMITTER: Gherardi G 

PROVIDER: S-EPMC6329801 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature