C5orf51 is a component of the MON1-CCZ1 complex and controls RAB7A localization and stability during mitophagy

• DOI: 10.1080/15548627.2021.1960116
• Publication Date: 2021-08-25T18:23:50Z
• Authors: Bing-Ru Yan; Taoyingnan Li; Etienne Coyaud; Estelle M. N. Lau...; Jonathan St-Germain; Yuhuan Zhou; Peter K. Kim; Brian Raught; John H. Brumell
• Keywords: PINK1; Rab

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