Nitric oxide inhibition of Drp1-mediated mitochondrial fission is critical for myogenic differentiation

C. De Palma, S. Falcone, S. Pisoni, S. Cipolat, C. Panzeri, S. Pambianco, A. Pisconti, R. Allevi, M. T. Bassi, G. Cossu, T. Pozzan, S. Moncada, L. Scorrano, S. Brunelli, E. Clementi

Research output: Contribution to journalArticle

Abstract

During myogenic differentiation the short mitochondria of myoblasts change into the extensively elongated network observed in myotubes. The functional relevance and the molecular mechanisms driving the formation of this mitochondrial network are unknown. We now show that mitochondrial elongation is required for myogenesis to occur and that this event depends on the cellular generation of nitric oxide (NO). Inhibition of NO synthesis in myogenic precursor cells leads to inhibition of mitochondrial elongation and of myogenic differentiation. This is due to the enhanced activity, translocation and docking of the pro-fission GTPase dynamin-related protein-1 (Drp1) to mitochondria, leading also to a latent mitochondrial dysfunction that increased sensitivity to apoptotic stimuli. These effects of NO inhibition were not observed in myogenic precursor cells containing a dominant-negative form of Drp1. Both NO-dependent repression of Drp1 action and maintenance of mitochondrial integrity and function were mediated through the soluble guanylate cyclase. These data uncover a novel level of regulation of differentiation linking mitochondrial morphology and function to myogenic differentiation.

Original languageEnglish
Pages (from-to)1684-1696
Number of pages13
JournalCell Death and Differentiation
Volume17
Issue number11
DOIs
Publication statusPublished - Nov 2010

Keywords

  • Drp1
  • mitochondrial fission
  • myogenesis
  • Nitric oxide

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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    De Palma, C., Falcone, S., Pisoni, S., Cipolat, S., Panzeri, C., Pambianco, S., Pisconti, A., Allevi, R., Bassi, M. T., Cossu, G., Pozzan, T., Moncada, S., Scorrano, L., Brunelli, S., & Clementi, E. (2010). Nitric oxide inhibition of Drp1-mediated mitochondrial fission is critical for myogenic differentiation. Cell Death and Differentiation, 17(11), 1684-1696. https://doi.org/10.1038/cdd.2010.48