{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Lee J"],"funding":["Intramural research program of the NIDDK","NINDS NIH HHS"],"pagination":["204-223"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9809949"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["19(1)"],"pubmed_abstract":["Mutations in <i>DNAJC5/CSPα</i> are associated with adult neuronal ceroid lipofuscinosis (ANCL), a dominant-inherited neurodegenerative disease featuring lysosome-derived autofluorescent <i>s</i>torage materials (AFSMs) termed lipofuscin. Functionally, DNAJC5 has been implicated in chaperoning synaptic proteins and in misfolding-associated protein secretion (MAPS), but how DNAJC5 dysfunction causes lipofuscinosis and neurodegeneration is unclear. Here we report two functionally distinct but coupled chaperoning activities of DNAJC5, which jointly regulate lysosomal homeostasis: While endolysosome-associated DNAJC5 promotes ESCRT-dependent microautophagy, a fraction of perinuclear and non-lysosomal DNAJC5 mediates MAPS. Functional proteomics identifies a previously unknown DNAJC5 interactor "],"journal":["Autophagy"],"pubmed_title":["Abnormal triaging of misfolded proteins by adult neuronal ceroid lipofuscinosis-associated DNAJC5/CSPα mutants causes lipofuscin accumulation."],"pmcid":["PMC9809949"],"funding_grant_id":["1R21NS117855-01","R21 NS117855"],"pubmed_authors":["Zinsmaier K","Xu M","Lee J","Ye Y","Saidi L","Xu Y"],"additional_accession":[]},"is_claimable":false,"name":"Abnormal triaging of misfolded proteins by adult neuronal ceroid lipofuscinosis-associated DNAJC5/CSPα mutants causes lipofuscin accumulation.","description":"Mutations in <i>DNAJC5/CSPα</i> are associated with adult neuronal ceroid lipofuscinosis (ANCL), a dominant-inherited neurodegenerative disease featuring lysosome-derived autofluorescent <i>s</i>torage materials (AFSMs) termed lipofuscin. Functionally, DNAJC5 has been implicated in chaperoning synaptic proteins and in misfolding-associated protein secretion (MAPS), but how DNAJC5 dysfunction causes lipofuscinosis and neurodegeneration is unclear. Here we report two functionally distinct but coupled chaperoning activities of DNAJC5, which jointly regulate lysosomal homeostasis: While endolysosome-associated DNAJC5 promotes ESCRT-dependent microautophagy, a fraction of perinuclear and non-lysosomal DNAJC5 mediates MAPS. Functional proteomics identifies a previously unknown DNAJC5 interactor ","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Jan","modification":"2026-04-29T03:20:20.716Z","creation":"2025-04-19T04:45:41.031Z"},"accession":"S-EPMC9809949","cross_references":{"pubmed":["35506243"],"doi":["10.1080/15548627.2022.2065618"]}}