Nitric Oxide Links Mitochondrial Fission to Alzheimer’s Disease

Benedikt Westermann^*

Institut für Zellbiologie and Bayreuther Zentrum für Molekulare Biowissenschaften, Universität Bayreuth, 95440 Bayreuth, Germany.

Abstract: Mitochondrial dysfunction is a hallmark of β-amyloid (Aβ)–induced neuronal injury in the pathogenesis of Alzheimer’s disease. Neurotoxic Aβ 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 Aβ 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. Aβ-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.

* Corresponding author. E-mail, benedikt.westermann{at}uni-bayreuth.de

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