biostudies-otherUnknownMs. Fumika KoyanoJSPS KAKENHIthe Chieko Iwanaga Fund for Parkinson's Disease ResearchOhsumi Frontier Science Foundationthe Takeda Science Foundationthe Joint Usage and Joint Research Programs, the Institute of Advanced Medical SciencesEMBO Reportshttps://www.ebi.ac.uk/biostudies/studies/S-SCDT-EMBOR-2019-47728-TUbiquitylation of outer mitochondrial membrane (OMM) proteins is closely related to the onset of familial Parkinson's disease. Typically, a reduction in the mitochondrial membrane potential results in Parkin-mediated ubiquitylation of OMM proteins, which are then targeted for proteasomal and mitophagic degradation. The role of ubiquitylation of OMM proteins with non-degradative fates, however, remains poorly understood. In this study, we find that the mitochondrial E3 ubiquitin ligase MITOL/March5 translocates from depolarized mitochondria to peroxisomes following mitophagy stimulation. This unusual redistribution is mediated by peroxins (peroxisomal biogenesis factors) Pex3/16 and requires the E3 ligase activity of Parkin, which ubiquitylates K268 in the MITOL C terminus, essential for p97/VCP-dependent mitochondrial extraction of MITOL. These findings imply that ubiquitylation directs peroxisomal translocation of MITOL upon mitophagy stimulation and reveal a novel role for ubiquitin as a sorting signal that allow certain specialized proteins to escape from damaged mitochondria.biostudies-otherJP16K18545JP26000014JP15K19037JP15K21743JP17H03675JP18K14708JP17K08635JP18H02443JP26116007JP18H05500JP18K06237Prof. Yoko KimuraMs. Mayumi KimuraDr. Keiji TanakaMs. Fumika KoyanoDr. Noriyuki MatsudaDr. Koji YamanoProf. Hidetaka KosakoProf. Yukio FujikifalseParkin-mediated ubiquitylation redistributes MITOL/March5 from mitochondria to peroxisomesUbiquitylation of outer mitochondrial membrane (OMM) proteins is closely related to the onset of familial Parkinson's disease. Typically, a reduction in the mitochondrial membrane potential results in Parkin-mediated ubiquitylation of OMM proteins, which are then targeted for proteasomal and mitophagic degradation. The role of ubiquitylation of OMM proteins with non-degradative fates, however, remains poorly understood. In this study, we find that the mitochondrial E3 ubiquitin ligase MITOL/March5 translocates from depolarized mitochondria to peroxisomes following mitophagy stimulation. This unusual redistribution is mediated by peroxins (peroxisomal biogenesis factors) Pex3/16 and requires the E3 ligase activity of Parkin, which ubiquitylates K268 in the MITOL C terminus, essential for p97/VCP-dependent mitochondrial extraction of MITOL. These findings imply that ubiquitylation directs peroxisomal translocation of MITOL upon mitophagy stimulation and reveal a novel role for ubiquitin as a sorting signal that allow certain specialized proteins to escape from damaged mitochondria.2020-02-13T21:00:10Z2020-02-13T21:00:10ZS-SCDT-EMBOR-2019-47728-T10.15252/embr.201947728