PINK1 is activated by mitochondrial membrane potential depolarization and stimulates Parkin E3 ligase activity by phosphorylating Serine 65
University of Dundee · MRC Protein Phosphorylation and Ubiquitylation Unit · +3 more institutions
Abstract
Missense mutations in PTEN-induced kinase 1 (PINK1) cause autosomal-recessive inherited Parkinson's disease (PD). We have exploited our recent discovery that recombinant insect PINK1 is catalytically active to test whether PINK1 directly phosphorylates 15 proteins encoded by PD-associated genes as well as proteins reported to bind PINK1. We have discovered that insect PINK1 efficiently phosphorylates only one of these proteins, namely the E3 ligase Parkin. We have mapped the phosphorylation site to a highly conserved residue within the Ubl domain of Parkin at Ser(65). We show that human PINK1 is specifically activated by mitochondrial membrane potential (Δψm) depolarization, enabling it to phosphorylate Parkin…
Citation impact
- FWCI
- 35.75
- Percentile
- 100%
- References
- 43
Authors
13- CKChandana KondapalliCorresponding
University of Dundee, MRC Protein Phosphorylation and Ubiquitylation Unit
- AKAgne Kazlauskaite
University of Dundee, MRC Protein Phosphorylation and Ubiquitylation Unit
- NZNing Zhang
University of Dundee, MRC Protein Phosphorylation and Ubiquitylation Unit
- HIHelen I. Woodroof
University of Dundee, MRC Protein Phosphorylation and Ubiquitylation Unit
- DGDavid G. Campbell
University of Dundee, MRC Protein Phosphorylation and Ubiquitylation Unit
Topics & keywords
- Parkin
- PINK1
- Biology
- Phosphorylation
- Ubiquitin ligase
- Cell biology
- Kinase
- Biochemistry