期刊
NATURE CELL BIOLOGY
卷 9, 期 11, 页码 1243-U63出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncb1644
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资金
- Medical Research Council [MC_U132674518, G0700183, G0400000] Funding Source: Medline
- Medical Research Council [G0700183, MC_U132674518, G0400000] Funding Source: researchfish
- MRC [G0400000, MC_U132674518, G0700183] Funding Source: UKRI
In mice, targeted deletion of the serine protease HtrA2 ( also known as Omi) causes mitochondrial dysfunction leading to a neurodegenerative disorder with parkinsonian features. In humans, point mutations in HtrA2 are a susceptibility factor for Parkinson's disease ( PARK13 locus). Mutations in PINK1, a putative mitochondrial protein kinase, are associated with the PARK6 autosomal recessive locus for susceptibility to early-onset Parkinson's disease. Here we determine that HtrA2 interacts with PINK1 and that both are components of the same stress-sensing pathway. HtrA2 is phosphorylated on activation of the p38 pathway, occurring in a PINK1-dependent manner at a residue adjacent to a position found mutated in patients with Parkinson's disease. HtrA2 phosphorylation is decreased in brains of patients with Parkinson's disease carrying mutations in PINK1. We suggest that PINK1-dependent phosphorylation of HtrA2 might modulate its proteolytic activity, thereby contributing to an increased resistance of cells to mitochondrial stress.
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