Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

The Mitochondrial Calcium Uniporter controls skeletal muscle mass in vivo

ABSTRACT: Muscle atrophy contributes to the poor prognosis of many physiopathological conditions, but pharmacological therapies are still limited. Muscle activity leads to major swings in mitochondrial [Ca2+] which control 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 coherently demonstrate that both in developing and in adult muscles MCU-dependent mitochondrial Ca2+ uptake has a marked trophic effect that does not depend on autophagy or aerobic control, but impinges on two major hypertrophic pathways of skeletal muscle, PGC-1M-NM-14 and Igf1-Akt/PKB. In adult mice, 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 sarcopenia. Experiments were performed on biological replicates of single skeletal muscle fibres. Seven fibres were chosen for their Mutochondrial Calcium Uniporter (MCU) overexpression and other seven fibres because MCU was silenced. Overexpression and silencing were performed injecting skeletal muscle with AAV containing MCU gene or short interfering oligos specific for MCU. As control was profiled eigth fibres transfected with AAV and eigth wild type fibres. Analyses were performed 7 days and 14 days after the AAV injection (3 fibers after 7 days and 4 fibers after 14 days for MCU overexpression and silencing, four fibres after 7 days and four after 14 days for control).

ORGANISM(S): Mus musculus

SUBMITTER: Gerolamo Lanfranchi

PROVIDER: E-GEOD-60931 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

The mitochondrial calcium uniporter controls skeletal muscle trophism in vivo.

Mammucari Cristina C Gherardi Gaia G Zamparo Ilaria I Raffaello Anna A Boncompagni Simona S Chemello Francesco F Cagnin Stefano S Braga Alessandra A Zanin Sofia S Pallafacchina Giorgia G Zentilin Lorena L Sandri Marco M De Stefani Diego D Protasi Feliciano F Lanfranchi Gerolamo G Rizzuto Rosario R

Cell reports 20150226 8

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 devel ...[more]

PMID: 25732818

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Dataset Information

The Mitochondrial Calcium Uniporter controls skeletal muscle mass in vivo

Publications

The mitochondrial calcium uniporter controls skeletal muscle trophism in vivo.

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