| Literature DB >> 16874299 |
Mark J Barsoum1, Hua Yuan, Akos A Gerencser, Géraldine Liot, Yulia Kushnareva, Simone Gräber, Imre Kovacs, Wilson D Lee, Jenna Waggoner, Jiankun Cui, Andrew D White, Blaise Bossy, Jean-Claude Martinou, Richard J Youle, Stuart A Lipton, Mark H Ellisman, Guy A Perkins, Ella Bossy-Wetzel.
Abstract
Mitochondria are present as tubular organelles in neuronal projections. Here, we report that mitochondria undergo profound fission in response to nitric oxide (NO) in cortical neurons of primary cultures. Mitochondrial fission by NO occurs long before neurite injury and neuronal cell death. Furthermore, fission is accompanied by ultrastructural damage of mitochondria, autophagy, ATP decline and generation of free radicals. Fission is occasionally asymmetric and can be reversible. Strikingly, mitochondrial fission is also an early event in ischemic stroke in vivo. Mitofusin 1 (Mfn1) or dominant-negative Dynamin related protein 1 (Drp1(K38A)) inhibits mitochondrial fission induced by NO, rotenone and Amyloid-beta peptide. Conversely, overexpression of Drp1 or Fis1 elicits fission and increases neuronal loss. Importantly, NO-induced neuronal cell death was mitigated by Mfn1 and Drp1(K38A). Thus, persistent mitochondrial fission may play a causal role in NO-mediated neurotoxicity.Entities:
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Year: 2006 PMID： 16874299 PMCID： PMC1553198 DOI： 10.1038/sj.emboj.7601253
Source DB: PubMed Journal: EMBO J ISSN： 0261-4189 Impact factor: 11.598