Abstract
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.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
-
Comment
MeSH terms
-
Humans
-
Intracellular Signaling Peptides and Proteins / genetics*
-
Intracellular Signaling Peptides and Proteins / metabolism
-
Mitochondria / metabolism
-
Oncogene Proteins / genetics*
-
Oncogene Proteins / metabolism
-
Oxidative Stress
-
Parkinson Disease / genetics*
-
Proteasome Endopeptidase Complex / metabolism
-
Protein Deglycase DJ-1
-
Ubiquitin-Protein Ligases / genetics*
-
Ubiquitin-Protein Ligases / metabolism
-
alpha-Synuclein / genetics*
-
alpha-Synuclein / metabolism
Substances
-
Intracellular Signaling Peptides and Proteins
-
Oncogene Proteins
-
SNCA protein, human
-
alpha-Synuclein
-
Ubiquitin-Protein Ligases
-
parkin protein
-
PARK7 protein, human
-
Protein Deglycase DJ-1
-
Proteasome Endopeptidase Complex