Pink1, Parkin, DJ-1 and mitochondrial dysfunction in Parkinson's disease.
Mutations in PARKIN, PTEN-induced kinase 1 (PINK1) and DJ-1 are found in autosomal recessive forms and some sporadic cases of Parkinson's disease. Recent work on these genes underscores the central importance of mitochondrial dysfunction and oxidative stress in Parkinson's disease. In particular, pink1 and parkin loss-of-function mutants in Drosophila show similar phenotypes, and pink1 acts upstream of parkin in a common genetic pathway to regulate mitochondrial function. DJ-1 has a role in oxidative stress protection, but a direct role of DJ-1 in mitochondrial function has not been fully established. Importantly, defects in mitochondrial function have also been identified in patients who carry both PINK1 and PARKIN mutations, and in those who have sporadic Parkinson's disease. Future studies of the biochemical interactions between Pink1 and Parkin, and identification of other components in this pathway, are likely to provide insight into Parkinson's disease pathogenesis, and might identify new therapeutic targets.
Dodson
Mark W
MW
Department of Neurology and Brain Research Institute, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Guo
Ming
M
D000818:Animals; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology*; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D000099202:PTEN-Induced Putative Kinase
D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases; D044767:Ubiquitin-Protein Ligases; D000099202:PTEN-Induced Putative Kinase; C111567:parkin protein; C105131:PARK7 protein, human