The Mitochondrial Calcium Uniporter Controls Skeletal Muscle Trophism In Vivo
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 De Stefani,
Feliciano Protasi,
Gerolamo Lanfranchi,
Rosario Rizzuto
Affiliations
Cristina Mammucari
Department of Biomedical Sciences, University of Padua, Padua 35131, Italy
Gaia Gherardi
Department of Biomedical Sciences, University of Padua, Padua 35131, Italy
Ilaria Zamparo
Department of Biomedical Sciences, University of Padua, Padua 35131, Italy
Anna Raffaello
Department of Biomedical Sciences, University of Padua, Padua 35131, Italy
Simona Boncompagni
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
Francesco Chemello
Department of Biology and CRIBI Biotechnology Center, University of Padua, Padua 35131, Italy
Stefano Cagnin
Department of Biology and CRIBI Biotechnology Center, University of Padua, Padua 35131, Italy
Alessandra Braga
Department of Biomedical Sciences, University of Padua, Padua 35131, Italy
Sofia Zanin
Department of Biomedical Sciences, University of Padua, Padua 35131, Italy
Giorgia Pallafacchina
Department of Biomedical Sciences, University of Padua, Padua 35131, Italy
Lorena Zentilin
International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste 34159, Italy
Marco Sandri
Department of Biomedical Sciences, University of Padua, Padua 35131, Italy
Diego De Stefani
Department of Biomedical Sciences, University of Padua, Padua 35131, Italy
Feliciano Protasi
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
Gerolamo Lanfranchi
Department of Biology and CRIBI Biotechnology Center, University of Padua, Padua 35131, Italy
Rosario Rizzuto
Department of Biomedical Sciences, University of Padua, Padua 35131, Italy
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 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 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.
