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Scientific article
Open access
English

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

Published inCell death and differentiation, vol. 17, no. 11, p. 1684-1696
Publication date2010
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.

Keywords
  • Animals
  • Apoptosis
  • *Cell Differentiation
  • Cell Respiration
  • Cyclic GMP/metabolism
  • Dynamins
  • GTP Phosphohydrolases/*metabolism
  • Guanylate Cyclase/metabolism
  • Immunoblotting
  • Mice
  • Microscopy, Confocal
  • Microscopy, Electron, Transmission
  • Microtubule-Associated Proteins/*metabolism
  • Mitochondria, Muscle/*metabolism/physiology/ultrastructure
  • Mitochondrial Proteins/metabolism
  • Muscle Development/*physiology
  • Myoblasts/*cytology/metabolism/ultrastructure
  • Nitric Oxide/biosynthesis/*metabolism
Citation (ISO format)
DE PALMA, C. et al. Nitric oxide inhibition of Drp1-mediated mitochondrial fission is critical for myogenic differentiation. In: Cell death and differentiation, 2010, vol. 17, n° 11, p. 1684–1696. doi: 10.1038/cdd.2010.48
Main files (1)
Article (Accepted version)
accessLevelPublic
Identifiers
ISSN of the journal1350-9047
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314downloads

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