The mitochondrial calcium uniporter controls skeletal muscle trophism in vivo

Cell Rep. 2015 Mar 3;10(8):1269-79. doi: 10.1016/j.celrep.2015.01.056. Epub 2015 Feb 26.


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 developing and adult muscles, MCU-dependent mitochondrial Ca(2+) 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 Ca(2+)-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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caffeine / pharmacology
  • Calcium / metabolism*
  • Calcium Channels / genetics
  • Calcium Channels / metabolism*
  • Insulin-Like Growth Factor I / metabolism
  • Ion Transport / drug effects
  • Male
  • Mice
  • Mitochondria / metabolism*
  • Mitochondria / ultrastructure
  • Muscle, Skeletal / chemistry
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism*
  • Muscular Atrophy / metabolism
  • Muscular Atrophy / physiopathology
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Signal Transduction
  • Transcription Factors / metabolism


  • Calcium Channels
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Ppargc1a protein, mouse
  • RNA, Small Interfering
  • Transcription Factors
  • insulin-like growth factor-1, mouse
  • mitochondrial calcium uniporter
  • Caffeine
  • Insulin-Like Growth Factor I
  • Proto-Oncogene Proteins c-akt
  • Calcium

Associated data

  • GEO/GSE60931