Nitric oxide links mitochondrial fission to Alzheimer's disease.
Mitochondrial dysfunction is a hallmark of beta-amyloid (Abeta)-induced neuronal injury in the pathogenesis of Alzheimer's disease. Neurotoxic Abeta peptide, thought to be a key mediator of Alzheimer's disease, may be imported into human brain mitochondria, where it inhibits key enzymes of respiratory metabolism. Nitric oxide (NO) produced in response to Abeta induces S-nitrosylation of the mitochondrial division protein, dynamin-related protein 1 (Drp-1), which leads to excessive mitochondrial fission, synaptic loss, and neuronal damage. Furthermore, brains of patients with Alzheimer's disease contain high amounts of S-nitrosylated Drp-1. Abeta-dependent mitochondrial fragmentation likely enhances the decline in bioenergetic capacity of damaged mitochondria and therefore contributes to neuronal injury and pathogenesis of Alzheimer's disease.
Westermann
Benedikt
B
Institut für Zellbiologie and Bayreuther Zentrum für Molekulare Biowissenschaften, Universität Bayreuth, 95440 Bayreuth, Germany. benedikt.westermann@uni-bayreuth.de
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D034281:Dynamins; D020558:GTP Phosphohydrolases / Q000378:metabolism; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism* / Q000502:physiology; D024101:Mitochondrial Proteins / Q000378:metabolism; D008954:Models, Biological; D009569:Nitric Oxide / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; D009569:Nitric Oxide; D020558:GTP Phosphohydrolases; C110768:DNM1L protein, human; D034281:Dynamins