
파킨 단백질의 유연한 링커 영역에 위치한 보존된 영역이 미토콘드리아 GTPase Miro1과의 상호작용에 필수적이며, 이를 통해 Miro1의 선호적인 유비퀴틴화가 설명된다.


coremsg

Mutations in the gene encoding for the E3 ubiquitin ligase Parkin have been linked to early-onset Parkinson’s disease. Besides many other cellular roles, Parkin is involved in clearance of damaged mitochondria via mitophagy - a process of particular importance in dopaminergic neurons. Upon mitochondrial damage, Parkin accumulates at the outer mitochondrial membrane and is activated, leading to ubiquitination of many mitochondrial substrates and recruitment of mitophagy effectors. While the activation mechanisms of autoinhibited Parkin have been extensively studied, it remains unknown how Parkin recognises its substrates for ubiquitination, and no substrate interaction site in Parkin has been reported. Here, we identify a conserved region in the flexible linker between the Ubl and RING0 domains of Parkin, which is indispensable for Parkin interaction with the mitochondrial GTPase Miro1. Our results explain the preferential targeting and ubiquitination of Miro1 by Parkin and provide a biochemical explanation for the presence of Parkin at the mitochondrial membrane prior to activation induced by mitochondrial damage. Our findings are important for understanding mitochondrial homeostasis and may inspire new therapeutic avenues for Parkinson’s disease.

### Competing Interest Statement

The authors have declared no competing interest.

A substrate-interacting region of Parkin directs ubiquitination of the mitochondrial GTPase Miro1

파킨슨병-초기-발병과-관련된-파킨-단백질의-기질-상호작용-영역이-미토콘드리아-gtpase-miro1의-유비퀴틴화를-지시한다


파킨슨병 초기 발병과 관련된 파킨 단백질의 기질 상호작용 영역이 미토콘드리아 GTPase Miro1의 유비퀴틴화를 지시한다
