Mitochondrial dysfunction and reactive oxygen species in excitotoxicity and apoptosis: implications for the pathogenesis of neurodegenerative diseases.
In recent years we have witnessed a major interest in the study of the role of mitochondria, not only as ATP producers through oxidative phosphorylation but also as regulators of intracellular Ca2+ homeostasis and endogenous producers of reactive oxygen species (ROS). Interestingly, the mitochondria have been also implicated as central executioners of cell death. Increased mitochondrial Ca2+ overload as a result of excitotoxicity has been associated with the generation of superoxide and may induce the release of proapoptotic mitochondrial proteins, proceeding through DNA fragmentation/condensation and culminating in cell demise by apoptosis and/or necrosis. In addition, these processes have been implicated in the pathogenesis of many neurodegenerative diseases, which share several features of cell death: selective brain areas undergo neurodegeneration, involving mitochondrial dysfunction (mitochondrial complexes are affected), loss of intracellular Ca2+ homeostasis, excitotoxicity, and the extracellular or intracellular accumulation of insoluble protein aggregates in the brain.
Institute of Biochemistry, Faculty of Medicine and Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal. acrego@cnc.cj.uc.pt
A Cristina
AC
Rego
Catarina R
CR
Oliveira
D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D006816:Huntington Disease / Q000378:metabolism / Q000473:pathology; D008928:Mitochondria / Q000502:physiology*; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000473:pathology*; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism*
D017382:Reactive Oxygen Species; D002118:Calcium