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Title

Nitric oxide inhibition of Drp1-mediated mitochondrial fission is critical for myogenic differentiation
Authors
De Palma, C.
Falcone, S.
Pisoni, S.
Cipolat, S.
Panzeri, C.
Pambianco, S.
Pisconti, A.
Allevi, R.
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Published in Cell Death and Differentiation. 2010, vol. 17, no. 11, p. 1684-1696
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
Identifiers
PMID: 20467441
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Article (Author postprint) - public document Free access
Other version: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3050583/pdf/ukmss-33559.pdf
Structures
Faculté de médecine / Section de médecine fondamentale / Département de physiologie cellulaire et métabolisme
Research group Les mitochondries dans la vie cellulaire (850)
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. https://archive-ouverte.unige.ch/unige:20620

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Deposited on : 2012-05-22

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