ATP citrate lyase improves mitochondrial function in skeletal muscle.
Cell Metab
; 21(6): 868-76, 2015 Jun 02.
Article
in En
| MEDLINE
| ID: mdl-26039450
ABSTRACT
Mitochondrial dysfunction is associated with skeletal muscle pathology, including cachexia, sarcopenia, and the muscular dystrophies. ATP citrate lyase (ACL) is a cytosolic enzyme that catalyzes mitochondria-derived citrate into oxaloacetate and acetyl-CoA. Here we report that activation of ACL in skeletal muscle results in improved mitochondrial function. IGF1 induces activation of ACL in an AKT-dependent fashion. This results in an increase in cardiolipin, thus increasing critical mitochondrial complexes and supercomplex activity, and a resultant increase in oxygen consumption and cellular ATP levels. Conversely, knockdown of ACL in myotubes not only reduces mitochondrial complex I, IV, and V activity but also blocks IGF1-induced increases in oxygen consumption. In vivo, ACL activity is associated with increased ATP. Activation of this IGF1/ACL/cardiolipin pathway combines anabolic signaling with induction of mechanisms needed to provide required ATP.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Oxygen Consumption
/
ATP Citrate (pro-S)-Lyase
/
Signal Transduction
/
Muscle Fibers, Skeletal
/
Citric Acid
/
Mitochondria, Muscle
Limits:
Humans
Language:
En
Journal:
Cell Metab
Journal subject:
METABOLISMO
Year:
2015
Document type:
Article
Affiliation country:
Switzerland
Publication country:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
/
US
/
USA