Impairing the Mitochondrial Fission and Fusion Balance: A New Mechanism of Neurodegeneration
Abbreviated Journal Title
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
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.
Mitochondria and Oxidative Stress in Neurodegenerative Disorders
"Impairing the Mitochondrial Fission and Fusion Balance: A New Mechanism of Neurodegeneration" (2008). Faculty Bibliography 2000s. 553.