PINK1 function in health and disease.
The role of mitochondria in sporadic Parkinson's disease (PD) has been debated for a little over 20 years since the description of complex I deficiency in the substantia nigra pars compacta (SNpc) of PD patients. However, the identification of recessive pathogenic mutations in the pink1 gene in familial PD cases firmly re-ignited interest in the pathophysiology of mitochondria in PD. PINK1 is a putative mitochondrial serine/threonine kinase, which protects cells against oxidative stress induced apoptosis. The mechanism by which this is achieved and the effect of the pathogenic mutations has been an area of intensive research over the past five years. Significant progress has been made and, in this review, we summarize the physiological roles that have been assigned to PINK1 and the potential mechanisms behind pathogenesis.
Deas
Emma
E
Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London WC1N3BG, UK.
Plun-Favreau
Helene
H
Wood
Nicholas W
NW
D000818:Animals; D017209:Apoptosis; D001692:Biological Transport; D020013:Calcium Signaling; D004195:Disease Models, Animal; D004331:Drosophila melanogaster / Q000235:genetics; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation; D009369:Neoplasms / Q000235:genetics; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000235:genetics*; D017510:Protein Folding; D011494:Protein Kinases / Q000235:genetics / Q000502:physiology*; D054875:Ubiquitination; D000099202:PTEN-Induced Putative Kinase
D011494:Protein Kinases; D000099202:PTEN-Induced Putative Kinase