TY - JOUR
T1 - The Mitochondrial Calcium Uniporter Controls Skeletal Muscle Trophism InVivo
AU - Mammucari, Cristina
AU - Gherardi, Gaia
AU - Zamparo, Ilaria
AU - Raffaello, Anna
AU - Boncompagni, Simona
AU - Chemello, Francesco
AU - Cagnin, Stefano
AU - Braga, Alessandra
AU - Zanin, Sofia
AU - Pallafacchina, Giorgia
AU - Zentilin, Lorena
AU - Sandri, Marco
AU - DeStefani, Diego
AU - Protasi, Feliciano
AU - Lanfranchi, Gerolamo
AU - Rizzuto, Rosario
N1 - Funding Information:
The authors are grateful to Stefano Schiaffino, Alessandra Zulian, and Denis Vecellio Reane for helpful discussion. This research was supported by grants from the European Union (ERC mitoCalcium, no. 294777 to R.R.); Italian Telethon Foundation (GPP10005A to R.R.; GGP13213 to F.P.); Italian Ministries of Health (Ricerca Finalizzata to R.R.); Italian Ministries of Education, University and Research (PRIN to R.R., FIRB to R.R., FIRB Futuro in Ricerca RBFR10EGVP_002 to C.M., and FIRB Futuro in Ricerca RBFR13A20K 2013 to S.B.); University of Padova (Progetto di Ateneo to C.M.); NIH (grant 1P01AG025532-01A1 to R.R.; subcontract of RO1 AR059646 to F.P.); Cariparo and Cariplo Foundations (to R.R.); and the Italian Association for Cancer Research (AIRC) (to R.R.).
Publisher Copyright:
© 2015 The Authors.
PY - 2015/3/3
Y1 - 2015/3/3
N2 - 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.
AB - 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.
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U2 - 10.1016/j.celrep.2015.01.056
DO - 10.1016/j.celrep.2015.01.056
M3 - Article
C2 - 25732818
AN - SCOPUS:84924613885
SN - 2211-1247
VL - 10
SP - 1269
EP - 1279
JO - Cell Reports
JF - Cell Reports
IS - 8
ER -