| First Author | Das S | Year | 2015 |
| Journal | Cell Metab | Volume | 21 |
| Issue | 6 | Pages | 868-76 |
| PubMed ID | 26039450 | Mgi Jnum | J:226125 |
| Mgi Id | MGI:5695815 | Doi | 10.1016/j.cmet.2015.05.006 |
| Citation | Das S, et al. (2015) ATP citrate lyase improves mitochondrial function in skeletal muscle. Cell Metab 21(6):868-76 |
| abstractText | 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. |
