ATP citrate lyase improves mitochondrial function in skeletal muscle.

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.

journal_name

Cell Metab

journal_title

Cell metabolism

authors

Das S,Morvan F,Jourde B,Meier V,Kahle P,Brebbia P,Toussaint G,Glass DJ,Fornaro M

doi

10.1016/j.cmet.2015.05.006

subject

Has Abstract

pub_date

2015-06-02 00:00:00

pages

868-76

issue

6

eissn

1550-4131

issn

1932-7420

pii

S1550-4131(15)00218-1

journal_volume

21

pub_type

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