Mitochondria, calcium and cell death: a deadly triad in neurodegeneration.
Mitochondrial Ca(2+) accumulation is a tightly controlled process, in turn regulating functions as diverse as aerobic metabolism and induction of cell death. The link between Ca(2+) (dys)regulation, mitochondria and cellular derangement is particularly evident in neurodegenerative disorders, in which genetic models and environmental factors allowed to identify common traits in the pathogenic routes. We will here summarize: i) the current view of mechanisms and functions of mitochondrial Ca(2+) homeostasis, ii) the basic principles of organelle Ca(2+) transport, iii) the role of Ca(2+) in neuronal cell death, and iv) the new information on the pathogenesis of Alzheimer's, Huntington's and Parkinson's diseases, highlighting the role of Ca(2+) and mitochondria.
Celsi
Fulvio
F
Department of Experimental and Diagnostic Medicine, Interdisciplinary Center for the Study of Inflammation, Italy.
Pizzo
Paola
P
Brini
Marisa
M
Leo
Sara
S
Fotino
Carmen
C
Pinton
Paolo
P
Rizzuto
Rosario
R
D000544:Alzheimer Disease / Q000473:pathology / Q000503:physiopathology; D002118:Calcium / Q000502:physiology*; D016923:Cell Death / Q000502:physiology*; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000473:pathology / Q000503:physiopathology; D008928:Mitochondria / Q000502:physiology*; D051336:Mitochondrial Membranes / Q000502:physiology; D009154:Mutation; D009410:Nerve Degeneration / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology; D009687:Nuclear Proteins / Q000235:genetics; D010300:Parkinson Disease / Q000473:pathology / Q000503:physiopathology; D053763:Presenilins / Q000502:physiology; D015398:Signal Transduction; D044767:Ubiquitin-Protein Ligases / Q000235:genetics
C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D053763:Presenilins; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D002118:Calcium