title: Mitochondrial involvement in neurodegenerative diseases.
abstract: The classical bioenergetical view of the involvement of mitochondria in neurogeneration is based on the fact that mitochondria are the central players of ATP synthesis in neurons and their failure leads to neuronal dysfunction and eventually to cell death. Mutations in at least 39 genes in inherited neurodegenerative disorders seem to alter directly or indirectly mitochondrial function. Most of these mutations do not directly affect oxidative phosphorylation, but act through disturbed mitochondrial dynamics and quality control. This, however, does not invalidate the bioenergetic hypothesis. Neurodegeneration is not necessarily associated with a gross failure of ATP production, but might rather be a consequence of local insufficiencies of ATP supply in critical compartments of neurons, like the presynaptic terminal. We hypothesize that slow disease progression, at least in a subgroup of neurodegenerative diseases, can be explained by the parallel action of subcellular ATP insufficiency and clonal expansion of somatic mitochondrial DNA mutations, and particularly deletions.
authors: Department of Epileptology and Life and Brain Center, University Bonn, Bonn, Germany.
authors: Gábor
authors: G
authors: Zsurka
authors: Wolfram S
authors: WS
authors: Kunz
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D016923:Cell Death; D004272:DNA, Mitochondrial; D018450:Disease Progression; D006801:Humans; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010085:Oxidative Phosphorylation; D018384:Oxidative Stress; D017729:Presynaptic Terminals / Q000378:metabolism* / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate