ATP Citrate Lyase Improves Mitochondrial Function in Skeletal Muscle
| Autor: | David J. Glass, Mara Fornaro, Frederic Morvan, Suman K. Das, Viktor Meier, Gauthier Toussaint, Benjamin Jourde, Peter Kahle, Pascale Brebbia |
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| Rok vydání: | 2015 |
| Předmět: |
ATP citrate lyase
Cardiolipins Physiology Muscle Fibers Skeletal ATP Citrate (pro-S)-Lyase Mitochondrion Citric Acid chemistry.chemical_compound Adenosine Triphosphate Oxygen Consumption Cardiolipin medicine Humans Citrate synthase Insulin-Like Growth Factor I Molecular Biology biology Myogenesis Skeletal muscle Cell Biology musculoskeletal system Mitochondria Muscle Cell biology surgical procedures operative medicine.anatomical_structure chemistry Biochemistry biology.protein human activities Adenosine triphosphate Signal Transduction |
| Zdroj: | Cell Metabolism. 21:868-876 |
| ISSN: | 1550-4131 |
| DOI: | 10.1016/j.cmet.2015.05.006 |
| Popis: | SummaryMitochondrial 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. |
| Databáze: | OpenAIRE |
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