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Cell Rep. 2015 Mar 3;10(8):1269-79. doi: 10.1016/j.celrep.2015.01.056. Epub 2015 Feb 26.

The mitochondrial calcium uniporter controls skeletal muscle trophism in vivo.

Author information

1
Department of Biomedical Sciences, University of Padua, Padua 35131, Italy. Electronic address: cristina.mammucari@unipd.it.
2
Department of Biomedical Sciences, University of Padua, Padua 35131, Italy.
3
Ce.S.I. (Center for Research on Ageing) and D.N.I.C.S. (Department of Neuroscience, Imaging and Clinical Sciences), University "G. D'Annunzio" of Chieti, Chieti 66100, Italy.
4
Department of Biology and CRIBI Biotechnology Center, University of Padua, Padua 35131, Italy.
5
Department of Biomedical Sciences, University of Padua, Padua 35131, Italy; Neuroscience Institute, National Research Council, Padua 35131, Italy.
6
International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste 34159, Italy.
7
Department of Biomedical Sciences, University of Padua, Padua 35131, Italy; Neuroscience Institute, National Research Council, Padua 35131, Italy; Dulbecco Telethon Institute at Venetian Institute of Molecular Medicine, Padua 35129, Italy; Telethon Institute of Genetics and Medicine (TIGEM), Naples 80131, Italy.
8
Department of Biomedical Sciences, University of Padua, Padua 35131, Italy; Neuroscience Institute, National Research Council, Padua 35131, Italy. Electronic address: rosario.rizzuto@unipd.it.

Abstract

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 [Ca(2+)], which control aerobic metabolism, cell death, and survival pathways. We investigated in vivo the effects of mitochondrial Ca(2+) homeostasis in skeletal muscle function and trophism by overexpressing or silencing the mitochondrial calcium uniporter (MCU). The results demonstrate that in both developing and adult muscles, MCU-dependent mitochondrial Ca(2+) 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 Ca(2+)-dependent organelle-to-nucleus signaling route that links mitochondrial function to the control of muscle mass and may represent a possible pharmacological target in conditions of muscle loss.

PMID:
25732818
PMCID:
PMC4351162
DOI:
10.1016/j.celrep.2015.01.056
[Indexed for MEDLINE]
Free PMC Article

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