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Miro proteins prime mitochondria for Parkin translocation and mitophagy
Author(s) -
Safiulina Dzhamilja,
Kuum Malle,
Choubey Vinay,
Gogichaishvili Nana,
Liiv Joanna,
Hickey Miriam A,
Cagalinec Michal,
Mandel Merle,
Zeb Akbar,
Liiv Mailis,
Kaasik Allen
Publication year - 2018
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201899384
Subject(s) - parkin , pink1 , mitophagy , biology , ubiquitin , ubiquitin ligase , mitochondrion , microbiology and biotechnology , autophagy , biochemistry , parkinson's disease , disease , medicine , apoptosis , pathology , gene
The Parkinson's disease‐associated protein kinase PINK 1 and ubiquitin ligase Parkin coordinate the ubiquitination of mitochondrial proteins, which marks mitochondria for degradation. Miro1, an atypical GTP ase involved in mitochondrial trafficking, is one of the substrates tagged by Parkin after mitochondrial damage. Here, we demonstrate that a small pool of Parkin interacts with Miro1 before mitochondrial damage occurs. This interaction does not require PINK 1, does not involve ubiquitination of Miro1 and also does not disturb Miro1 function. However, following mitochondrial damage and PINK 1 accumulation, this initial pool of Parkin becomes activated, leading to the ubiquitination and degradation of Miro1. Knockdown of Miro proteins reduces Parkin translocation to mitochondria and suppresses mitophagic removal of mitochondria. Moreover, we demonstrate that Miro1 EF ‐hand domains control Miro1's ubiquitination and Parkin recruitment to damaged mitochondria, and they protect neurons from glutamate‐induced mitophagy. Together, our results suggest that Miro1 functions as a calcium‐sensitive docking site for Parkin on mitochondria.