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ATP Citrate Lyase Improves Mitochondrial Function in Skeletal Muscle

Das, Suman and Morvan, Frederic and Jourde, Benjamin and Meier, Viktor and Brebbia, Pascale and Toussaint, Gauthier and Glass, David and Fornaro, Mara (2015) ATP Citrate Lyase Improves Mitochondrial Function in Skeletal Muscle. Cell Metabolism (6). pp. 868-876.

Abstract

Mitochondrial dysfunction is associated with skeletal muscle pathologies: cancer cachexia, sarcopenia, and the muscular dystrophies. Here we report that activation of ATP citrate lyase (ACL) in skeletal muscle results in improved mitochondrial function. IGF-1 can induce activation of ACL in an AKT-dependent fashion. This results in an increase in cardiolipin, thus increasing critical mitochondrial complexes and super–complex activity, improving mitochondrial function - determined by measuring oxygen consumption and cellular ATP levels. Conversely, knock-down of ACL in myotubes not only reduces mitochondrial complex I, IV and V activity but also blocks IGF-1-induced increases in oxygen consumption. In vivo, ACL activity is associated with increased ATP as well. These findings demonstrate for the first time the role of ACL in regulating skeletal muscle mitochondrial function; activation of this pathway combines anabolic signaling with induction of mechanisms needed to provide required ATP.

Item Type: Article
Date Deposited: 13 Oct 2015 13:12
Last Modified: 13 Oct 2015 13:12
URI: https://oak.novartis.com/id/eprint/23908

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