Mitochondrial fragmentation in neurodegeneration.
Mitochondria are remarkably dynamic organelles that migrate, divide and fuse. Cycles of mitochondrial fission and fusion ensure metabolite and mitochondrial DNA mixing and dictate organelle shape, number and bioenergetic functionality. There is mounting evidence that mitochondrial dysfunction is an early and causal event in neurodegeneration. Mutations in the mitochondrial fusion GTPases mitofusin 2 and optic atrophy 1, neurotoxins and oxidative stress all disrupt the cable-like morphology of functional mitochondria. This results in impaired bioenergetics and mitochondrial migration, and can trigger neurodegeneration. These findings suggest potential new treatment avenues for neurodegenerative diseases.
Knott
Andrew B
AB
Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, 4000 Central Florida Boulevard, Orlando, Florida 32816, USA.
Perkins
Guy
G
Schwarzenbacher
Robert
R
Bossy-Wetzel
Ella
E
D000818:Animals; D006801:Humans; D008561:Membrane Fusion / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism / Q000648:ultrastructure; D051336:Mitochondrial Membranes / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D018384:Oxidative Stress; D011487:Protein Conformation; D017382:Reactive Oxygen Species / Q000378:metabolism
D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species