title: S-nitrosylation of Drp1 links excessive mitochondrial fission to neuronal injury in neurodegeneration.
abstract: Neurons are known to use large amounts of energy for their normal function and activity. In order to meet this demand, mitochondrial fission, fusion, and movement events (mitochondrial dynamics) control mitochondrial morphology, facilitating biogenesis and proper distribution of mitochondria within neurons. In contrast, dysfunction in mitochondrial dynamics results in reduced cell bioenergetics and thus contributes to neuronal injury and death in many neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease, and Huntington's disease. We recently reported that amyloid-beta peptide, thought to be a key mediator of AD pathogenesis, engenders S-nitrosylation and thus hyperactivation of the mitochondrial fission protein Drp1. This activation leads to excessive mitochondrial fragmentation, bioenergetic compromise, and synaptic damage in models of AD. Here, we provide an extended commentary on our findings of nitric oxide-mediated abnormal mitochondrial dynamics.
authors.affiliation: Del E. Webb Center for Neuroscience, Aging, and Stem Cell Research, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Nakamura
authors.forename: Piotr
authors.initials: P
authors.lastname: Cieplak
authors.forename: Dong-Hyung
authors.initials: DH
authors.lastname: Cho
authors.forename: Adam
authors.initials: A
authors.lastname: Godzik
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Lipton
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology; D034281:Dynamins; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000473:pathology*; D009474:Neurons / Q000473:pathology*; D009569:Nitric Oxide / Q000378:metabolism*
chemical_list: D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; D009569:Nitric Oxide; D020558:GTP Phosphohydrolases; C110768:DNM1L protein, human; D034281:Dynamins
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