MCUb is an inducible regulator of calcium-dependent mitochondrial metabolism and substrate utilization in muscle.
Cell Rep
; 42(11): 113465, 2023 11 28.
Article
en En
| MEDLINE
| ID: mdl-37976157
ABSTRACT
Mitochondria use the electron transport chain to generate high-energy phosphate from oxidative phosphorylation, a process also regulated by the mitochondrial Ca2+ uniporter (MCU) and Ca2+ levels. Here, we show that MCUb, an inhibitor of MCU-mediated Ca2+ influx, is induced by caloric restriction, where it increases mitochondrial fatty acid utilization. To mimic the fasted state with reduced mitochondrial Ca2+ influx, we generated genetically altered mice with skeletal muscle-specific MCUb expression that showed greater fatty acid usage, less fat accumulation, and lower body weight. In contrast, mice lacking Mcub in skeletal muscle showed increased pyruvate dehydrogenase activity, increased muscle malonyl coenzyme A (CoA), reduced fatty acid utilization, glucose intolerance, and increased adiposity. Mechanistically, pyruvate dehydrogenase kinase 4 (PDK4) overexpression in muscle of Mcub-deleted mice abolished altered substrate preference. Thus, MCUb is an inducible control point in regulating skeletal muscle mitochondrial Ca2+ levels and substrate utilization that impacts total metabolic balance.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Calcio
/
Mitocondrias
Límite:
Animals
Idioma:
En
Año:
2023
Tipo del documento:
Article