Impairing the Mitochondrial Fission and Fusion Balance: A New Mechanism of Neurodegeneration

    Authors

    A. B. Knott;E. Bossy-Wetzel

    Comments

    Authors: contact us about adding a copy of your work at STARS@ucf.edu

    Abbreviated Journal Title

    Ann.NY Acad.Sci.

    Keywords

    Huntington's disease; Parkinson's disease; GTPases; OPA1; mitofusins; Drp1; PINK1; parkin; DOMINANT OPTIC ATROPHY; DYNAMIN-RELATED PROTEIN; PARKINSONS-DISEASE; HUNTINGTONS-DISEASE; ALZHEIMERS-DISEASE; MUTANT HUNTINGTIN; CORTICAL-NEURONS; ALPHA-SYNUCLEIN; CELL-DEATH; INDUCED APOPTOSIS; Cell Biology; Multidisciplinary Sciences; Neurosciences; Physiology

    Abstract

    Mitochondrial dysfunction is a common characteristic of all neurodegenerative diseases. However, the cause of this dysfunction remains a mystery. Here, we discuss the potential role of mitochondrial fission and fusion in the onset and progression of neurodegenerative diseases. Specifically, we propose that an imbalance in mitochondrial fission and fusion may underlie both familial and sporadic neurodegenerative disorders. There is substantial evidence that links disruption of the mitochondrial fission and fusion equilibrium, resulting in abnormally long or short mitochondria, to neurodegeneration. First, hereditary mutations in the mitochondrial fusion GTPases optic atrophy-1 and mitofusin-2 cause neuropathics in humans. In addition, recent findings report increased mitochondrial fission in Parkinson's disease (PD) models and induction of mitochondrial fission by two proteins, PTEN-induced kinase 1 and parkin, which are mutant in familial forms of PD. Furthermore, mutant hunting-tin, the disease-causing protein in Huntington's disease, alters mitochondrial morphology and dynamics. Rotenone, a pesticide and inducer of PD symptoms, and amyloid-beta peptide, which is causally linked to Alzheimer's disease, initiate mitochondrial fission. Finally, mitochondrial fission is an early event in ischemic stroke and diabetic neuropathics. In sum, a growing body of research suggests that a better understanding of mitochondrial fission and fusion and the regulatory factors involved may lead to improved treatments and cures for neurodegenerative diseases.

    Journal Title

    Mitochondria and Oxidative Stress in Neurodegenerative Disorders

    Volume

    1147

    Publication Date

    1-1-2008

    Document Type

    Article

    Language

    English

    First Page

    283

    Last Page

    292

    WOS Identifier

    WOS:000262397800026

    ISSN

    0077-8923; 978-1-57331-713-9

    Share

    COinS