C5orf51 is a component of the MON1-CCZ1 complex and controls RAB7A localization and stability during mitophagy.
Autophagy
; 18(4): 829-840, 2022 04.
Article
em En
| MEDLINE
| ID: mdl-34432599
ABSTRACT
Depolarized mitochondria can be degraded via mitophagy, a selective form of autophagy. The RAB GTPase RAB7A was recently shown to play a key role in this process. RAB7A regulates late endocytic trafficking under normal growth conditions but is translocated to the mitochondrial surface following depolarization. However, how RAB7A activity is regulated during mitophagy is not understood. Here, using a proximity-dependent biotinylation approach (miniTurbo), we identified C5orf51 as a specific interactor of GDP-locked RAB7A. C5orf51 also interacts with the RAB7A guanine nucleotide exchange factor (GEF) complex members MON1 and CCZ1. In the absence of C5orf51, localization of RAB7A on depolarized mitochondria is compromised and the protein is degraded by the proteasome. Furthermore, depletion of C5orf51 also inhibited ATG9A recruitment to depolarized mitochondria. Together, these results indicate that C5orf51 is a positive regulator of RAB7A in its shuttling between late endosomes and mitochondria to enable mitophagy.Abbreviations ATG9A autophagy related 9A; Baf A1 bafilomycin A1; BioID proximity-dependent biotin identification; CCCP carbonyl cyanide m-chlorophenylhydrazone; CCZ1 CCZ1 homolog, vacuolar protein trafficking and biogenesis associated; DQ-BSA dye quenched-bovine serum albumin; FYCO1 FYVE and coiled-coil domain autophagy adaptor 1; GAP GTPase activating protein; GEF guanine nucleotide exchange factor; KO knockout; LRPPRC leucine rich pentatricopeptide repeat containing; MG132 carbobenzoxy-Leu-Leu-leucinal; MON1 MON1 homolog, secretory trafficking associated; mtDNA mitochondrial DNA; PINK1 PTEN induced kinase 1; PRKN/PARKIN parkin RBR E3 ubiquitin protein ligase; RMC1 regulator of MON1-CCZ1; TBC1D15 TBC1 domain family member 15; TBC1D17 TBC1 domain family member 17; TOMM20 translocase of outer mitochondrial membrane 20; WDR91 WD repeat domain 91; WT wild type.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Autofagia
/
Mitofagia
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Autophagy
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Canadá