Protein degradation in Parkinson disease revisited: it's complex.
Mutations in the genes PTEN-induced putative kinase 1 (PINK1), PARKIN,and DJ-1 cause autosomal recessive forms of Parkinson disease (PD), and the Pink1/Parkin pathway regulates mitochondrial integrity and function.An important question is whether the proteins encoded by these genes function to regulate activities of other cellular compartments. A study in mice,reported by Xiong et al. in this issue of the JCI, demonstrates that Pink1,Parkin, and DJ-1 can form a complex in the cytoplasm, with Pink1 and DJ-1 promoting the E3 ubiquitin ligase activity of Parkin to degrade substrates via the proteasome. This protein complex in the cytosol may or may not be related to the role of these proteins in regulating mitochondrial function or oxidative stress in vivo.
Li
Han
H
UCLA ACCESS Graduate Program and Department of Neurology, David Geffen School of Medicine and Molecular Biology Institute, University of California-Los Angeles, 695 Charles Young Drive South, Los Angeles, CA 90095, USA
Guo
Ming
M
D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D015513:Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000235:genetics*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D000071617:Protein Deglycase DJ-1; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000378:metabolism; D051844:alpha-Synuclein / Q000235:genetics* / Q000378:metabolism
D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; C497604:SNCA protein, human; D051844:alpha-Synuclein; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1; D046988:Proteasome Endopeptidase Complex