biostudies-literatureSwords SBNational Institute of Neurological Disorders and StrokeNINDS NIH HHSNational Institutes of HealthNIGMS NIH HHS792-808https://www.ebi.ac.uk/biostudies/studies/S-EPMC11062384biostudies-literatureUnknown20(4)Autophagosomes fuse with lysosomes, forming autolysosomes that degrade engulfed cargo. To maintain lysosomal capacity, autophagic lysosome reformation (ALR) must regenerate lysosomes from autolysosomes using a membrane tubule-based process. Maintaining lysosomal capacity is required to maintain cellular health, especially in neurons where lysosomal dysfunction has been repeatedly implicated in neurodegenerative disease. The DNA-J domain HSC70 co-chaperone RME-8/DNAJC13 has been linked to endosomal coat protein regulation and to neurological disease. We report new analysis of the requirements for the RME-8/DNAJC13 protein in neurons, focusing on intact <i>C. elegans</i> mechanosensory neurons, and primary mouse cortical neurons in culture. Loss of RME-8/DNAJC13 in both systems results in acAutophagyA conserved requirement for RME-8/DNAJC13 in neuronal autophagic lysosome reformation.PMC11062384F31 NS117034R01 NS0897375R01GM135326R01 GM1353265R01NS089737F31NS117034Modi JCai QJia NNorris ASwords SBGrant BDfalseA conserved requirement for RME-8/DNAJC13 in neuronal autophagic lysosome reformation.Autophagosomes fuse with lysosomes, forming autolysosomes that degrade engulfed cargo. To maintain lysosomal capacity, autophagic lysosome reformation (ALR) must regenerate lysosomes from autolysosomes using a membrane tubule-based process. Maintaining lysosomal capacity is required to maintain cellular health, especially in neurons where lysosomal dysfunction has been repeatedly implicated in neurodegenerative disease. The DNA-J domain HSC70 co-chaperone RME-8/DNAJC13 has been linked to endosomal coat protein regulation and to neurological disease. We report new analysis of the requirements for the RME-8/DNAJC13 protein in neurons, focusing on intact <i>C. elegans</i> mechanosensory neurons, and primary mouse cortical neurons in culture. Loss of RME-8/DNAJC13 in both systems results in ac2024-01-01T00:00:00Z2024 Apr2026-07-16T15:04:58.15Z2025-04-04T14:40:28.429ZS-EPMC110623843794290210.1080/15548627.2023.2269028