Parkinson, cancer, type 2 diabetes share a key element that drives disease
This study talk about Parkinson's, cancer, type 2 diabetes share a key element that drives disease written by Chien-Min Hung and Al.
Credit: Salk Institute
The Scope is: The serine/threonine kinase ULK1 mediates autophagy initiation in response to various cellular stresses, and genetic deletion of ULK1 leads to accumulation of damaged mitochondria. Here we identify Parkin, the core ubiquitin ligase in mitophagy, and PARK2 gene product mutated in familial Parkinson’s disease, as a ULK1 substrate.
In conclusion: This study has identified Ser108 as a novel site of Parkin regulation directly downstream of AMPK/ULK1 pathway activation and forces a revision of dogma regarding when and where Parkin function may be important. The ability of ULK1 to phosphorylate Ser108 in the Parkin ACT element following even mild mitochondrial stresses—including metformin—begets questions of whether this event serves as an “early alert signal” of mitochondrial damage and may play a surveillance/proteostatic role in some biological contexts by modulating Parkin interactions before full Parkin catalytic activation.
