Gherardi 2015 Abstract MiPschool London 2015
|The mitochondrial calcium uniporter controls skeletal muscle trophism in vivo.|
Event: MiPschool London 2015
Muscle atrophy contributes to the poor prognosis of many pathophysiological conditions, but pharmacological therapies are still limited . Muscle activity leads to major swings in mitochondrial [Ca2+] which controls aerobic metabolism, cell death and survival pathways.
We have investigated in vivo the effects of mitochondrial Ca2+ homeostasis in skeletal muscle function and trophism, by overexpressing or silencing the Mitochondrial Calcium Uniporter (MCU) . The results demonstrate that both in developing and in adult muscles MCU-dependent mitochondrial Ca2+ uptake has a marked trophic effect that does not depend on aerobic control, but impinges on two major hypertrophic pathways of skeletal muscle, PGC-1α4  and IGF1-AKT/PKB . In addition, MCU overexpression protects from denervation-induced atrophy. These data reveal a novel Ca2+-dependent organelle-to-nucleus signaling route, which links mitochondrial function to the control of muscle mass and may represent a possible pharmacological target in conditions of muscle loss.
• Keywords: MCU, Muscle atrophy
Tissue;cell: Skeletal muscle
1-Dept Biomed Sc, Univ Padua. - [email protected]
2-Ce.S.I. -Center Research Ageing D.N.I.C.S. -Dept Neurosc, Imaging Clinical Sc, Univ "G. D'Annunzio" Chieti
3-Dept Biology CRIBI Biotechnology Center, Univ Padua
4-Neuroscience Inst, Nat Research Council, Padua
5-Internat Centre Genetic Engineering Biotechnology (ICGEB), Trieste
6-Dulbecco Telethon Inst Venetian Inst Mol Med, Padua
7-Telethon Inst Genetics Med (TIGEM)
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