{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Zheng J"],"funding":["Tsinghua University","Ministry of Science and Technology of the People's Republic of China","National Natural Science Foundation of China"],"pagination":["e54859"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9535754"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["23(10)"],"pubmed_abstract":["The hexameric AAA-ATPase valosin-containing protein (VCP) is essential for mitochondrial protein quality control. How VCP is recruited to mammalian mitochondria remains obscure. Here we report that UBXD8, an ER- and lipid droplet-localized VCP adaptor, also localizes to mitochondria and locally recruits VCP. UBXD8 associates with mitochondrial and ER ubiquitin E3 ligases and targets their substrates for degradation. Remarkably, both mitochondria- and ER-localized UBXD8 can degrade mitochondrial and ER substrates in cis and in trans. UBXD8 also associates with the TOM complex but is dispensable for translocation-associated degradation. UBXD8 knockout impairs the degradation of the pro-survival protein Mcl1 but surprisingly sensitizes cells to apoptosis and mitochondrial stresses. UBXD8 knoc"],"journal":["EMBO reports"],"pubmed_title":["UBXD8 mediates mitochondria-associated degradation to restrain apoptosis and mitophagy."],"pmcid":["PMC9535754"],"funding_grant_id":["31871346"],"pubmed_authors":["Zheng J","Yang J","Cao Y","Jiang H"],"additional_accession":[]},"is_claimable":false,"name":"UBXD8 mediates mitochondria-associated degradation to restrain apoptosis and mitophagy.","description":"The hexameric AAA-ATPase valosin-containing protein (VCP) is essential for mitochondrial protein quality control. How VCP is recruited to mammalian mitochondria remains obscure. Here we report that UBXD8, an ER- and lipid droplet-localized VCP adaptor, also localizes to mitochondria and locally recruits VCP. UBXD8 associates with mitochondrial and ER ubiquitin E3 ligases and targets their substrates for degradation. Remarkably, both mitochondria- and ER-localized UBXD8 can degrade mitochondrial and ER substrates in cis and in trans. UBXD8 also associates with the TOM complex but is dispensable for translocation-associated degradation. UBXD8 knockout impairs the degradation of the pro-survival protein Mcl1 but surprisingly sensitizes cells to apoptosis and mitochondrial stresses. UBXD8 knoc","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Oct","modification":"2026-07-14T15:36:41.641Z","creation":"2025-04-04T20:06:59.449Z"},"accession":"S-EPMC9535754","cross_references":{"pubmed":["35979733"],"doi":["10.15252/embr.202254859"]}}