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 journalArticlepeer-review


    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. © 2010 Macmillan Publishers Limited All rights reserved.
    Original languageEnglish
    Pages (from-to)1684-1696
    Number of pages12
    JournalCell Death and Differentiation
    Issue number11
    Publication statusPublished - Nov 2010


    • Drp1
    • mitochondrial fission
    • myogenesis
    • Nitric oxide


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