The Mitochondrial Calcium Uniporter Controls Skeletal Muscle Trophism InVivo

Cristina Mammucari, Gaia Gherardi, Ilaria Zamparo, Anna Raffaello, Simona Boncompagni, Francesco Chemello, Stefano Cagnin, Alessandra Braga, Sofia Zanin, Giorgia Pallafacchina, Lorena Zentilin, Marco Sandri, Diego DeStefani, Feliciano Protasi, Gerolamo Lanfranchi, Rosario Rizzuto

Research output: Contribution to journalArticlepeer-review

130 Scopus citations


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 control aerobic metabolism, cell death, and survival pathways. We investigated invivo 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 in both developing and 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 that links mitochondrial function to the control of muscle mass and may represent a possible pharmacological target in conditions of muscle loss.

Original languageEnglish (US)
Pages (from-to)1269-1279
Number of pages11
JournalCell Reports
Issue number8
StatePublished - Mar 3 2015
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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