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.
Rego
A Cristina
AC
Institute of Biochemistry, Faculty of Medicine and Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal. acrego@cnc.cj.uc.pt
Oliveira
Catarina R
CR
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