The Mitochondrial Calcium Uniporter Controls Skeletal Muscle Trophism In Vivo

The Mitochondrial Calcium Uniporter Controls Skeletal Muscle Trophism In Vivo

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 eff...

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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2015-03-01
Series:Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124715000984
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spelling doaj-f0b0c13e9086456a9f7009a14749ce3e2020-11-24T21:29:17ZengElsevierCell Reports2211-12472015-03-011081269127910.1016/j.celrep.2015.01.056The Mitochondrial Calcium Uniporter Controls Skeletal Muscle Trophism In VivoCristina Mammucari0Gaia Gherardi1Ilaria Zamparo2Anna Raffaello3Simona Boncompagni4Francesco Chemello5Stefano Cagnin6Alessandra Braga7Sofia Zanin8Giorgia Pallafacchina9Lorena Zentilin10Marco Sandri11Diego De Stefani12Feliciano Protasi13Gerolamo Lanfranchi14Rosario Rizzuto15Department of Biomedical Sciences, University of Padua, Padua 35131, ItalyDepartment of Biomedical Sciences, University of Padua, Padua 35131, ItalyDepartment of Biomedical Sciences, University of Padua, Padua 35131, ItalyDepartment of Biomedical Sciences, University of Padua, Padua 35131, ItalyCe.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, ItalyDepartment of Biology and CRIBI Biotechnology Center, University of Padua, Padua 35131, ItalyDepartment of Biology and CRIBI Biotechnology Center, University of Padua, Padua 35131, ItalyDepartment of Biomedical Sciences, University of Padua, Padua 35131, ItalyDepartment of Biomedical Sciences, University of Padua, Padua 35131, ItalyDepartment of Biomedical Sciences, University of Padua, Padua 35131, ItalyInternational Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste 34159, ItalyDepartment of Biomedical Sciences, University of Padua, Padua 35131, ItalyDepartment of Biomedical Sciences, University of Padua, Padua 35131, ItalyCe.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, ItalyDepartment of Biology and CRIBI Biotechnology Center, University of Padua, Padua 35131, ItalyDepartment of Biomedical Sciences, University of Padua, Padua 35131, ItalyMuscle 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.http://www.sciencedirect.com/science/article/pii/S2211124715000984
collection DOAJ
language English
format Article
sources DOAJ
author 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
spellingShingle 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
The Mitochondrial Calcium Uniporter Controls Skeletal Muscle Trophism In Vivo
Cell Reports
author_facet 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
author_sort Cristina Mammucari
title The Mitochondrial Calcium Uniporter Controls Skeletal Muscle Trophism In Vivo
title_short The Mitochondrial Calcium Uniporter Controls Skeletal Muscle Trophism In Vivo
title_full The Mitochondrial Calcium Uniporter Controls Skeletal Muscle Trophism In Vivo
title_fullStr The Mitochondrial Calcium Uniporter Controls Skeletal Muscle Trophism In Vivo
title_full_unstemmed The Mitochondrial Calcium Uniporter Controls Skeletal Muscle Trophism In Vivo
title_sort mitochondrial calcium uniporter controls skeletal muscle trophism in vivo
publisher Elsevier
series Cell Reports
issn 2211-1247
publishDate 2015-03-01
description 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.
url http://www.sciencedirect.com/science/article/pii/S2211124715000984
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