Gherardi 2015 Abstract MiPschool London 2015

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The mitochondrial calcium uniporter controls skeletal muscle trophism in vivo.

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Gherardi G, Mammucari C, Zamparo I, Raffaello A, Boncompagni S, Chemello F, Cagnin S, Braga A, Zanin S, Pallafacchina G, Zentilin L, Sandri M, De Stefani D, Protasi F, Lanfranchi G, Rizzuto R (2015)

Event: MiPschool London 2015

Muscle atrophy contributes to the poor prognosis of many pathophysiological conditions, but pharmacological therapies are still limited [1]. Muscle activity leads to major swings in mitochondrial [Ca2+] which controls aerobic metabolism, cell death and survival pathways.

We have investigated in vivo the effects of mitochondrial Ca2+ homeostasis in skeletal muscle function and trophism, by overexpressing or silencing the Mitochondrial Calcium Uniporter (MCU) [2]. The results demonstrate that both in developing and in 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 [3] and IGF1-AKT/PKB [4]. In addition, MCU overexpression protects from denervation-induced atrophy. These data reveal a novel Ca2+-dependent organelle-to-nucleus signaling route, which links mitochondrial function to the control of muscle mass and may represent a possible pharmacological target in conditions of muscle loss.

Keywords: MCU, Muscle atrophy


Labels:


Tissue;cell: Skeletal muscle 


Regulation: Calcium 




Affiliations

1-Dept Biomed Sc, Univ Padua. - gaia.gherardi@studenti.unipd.it

2-Ce.S.I. -Center Research Ageing D.N.I.C.S. -Dept Neurosc, Imaging Clinical Sc, Univ "G. D'Annunzio" Chieti

3-Dept Biology CRIBI Biotechnology Center, Univ Padua

4-Neuroscience Inst, Nat Research Council, Padua

5-Internat Centre Genetic Engineering Biotechnology (ICGEB), Trieste

6-Dulbecco Telethon Inst Venetian Inst Mol Med, Padua

7-Telethon Inst Genetics Med (TIGEM)

Italy

References

  1. Glass D, Roubenoff R (2010) Recent advances in the biology and therapy of muscle wasting. Ann N Y Acad Sci 1211:25-36.
  2. De Stefani D, Raffaello A, Teardo E, Szabo I, Rizzuto R (2011) A forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter. Nature 476:336-40.
  3. Ruas JL, White JP, Rao RR, Kleiner S, Brannan KT, Harrison BC, Greene NP, Wu J, Estall JL, Irving BA, Lanza IR, Rasbach KA, Okutsu M, Nair KS, Yan Z, Leinwand LA, Spiegelman BM (2012) A PGC-1alpha isoform induced by resistance training regulates skeletal muscle hypertrophy. Cell 151:1319-31.
  4. Schiaffino S, Mammucari C (2011) Regulation of skeletal muscle growth by the IGF1-Akt/PKB pathway: insights from genetic models. Skelet Muscle 1:4.