{"doi":"10.1038/s41593-024-01619-1","title":"Messenger RNA transport on lysosomal vesicles maintains axonal mitochondrial homeostasis and prevents axonal degeneration","abstract":"In neurons, RNA granules are transported along the axon for local translation away from the soma. Recent studies indicate that some of this transport involves hitchhiking of RNA granules on lysosome-related vesicles. In the present study, we leveraged the ability to prevent transport of these vesicles into the axon by knockout of the lysosome-kinesin adaptor BLOC-one-related complex (BORC) to identify a subset of axonal mRNAs that depend on lysosome-related vesicles for transport. We found that BORC knockout causes depletion of a large group of axonal mRNAs mainly encoding ribosomal and mitochondrial/oxidative phosphorylation proteins. This depletion results in mitochondrial defects and eventually leads to axonal degeneration in human induced pluripotent stem cell (iPSC)-derived and mouse neurons. Pathway analyses of the depleted mRNAs revealed a mechanistic connection of BORC deficiency with common neurodegenerative disorders. These results demonstrate that mRNA transport on lysosome-related vesicles is critical for the maintenance of axonal homeostasis and that its failure causes axonal degeneration.","journal":"Nature Neuroscience","year":2024,"id":417208,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":77,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9592,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":854414,"name":"Saikat Ghosh","orcid":"0000-0001-6517-8377","position":1,"is_corresponding":false},{"id":303968,"name":"Veronica H. Ryan","orcid":"0000-0001-5121-4672","position":2,"is_corresponding":false},{"id":457823,"name":"Mira Sohn","orcid":null,"position":3,"is_corresponding":false},{"id":321537,"name":"Michal Jarník","orcid":"0000-0002-1269-3508","position":4,"is_corresponding":false},{"id":303022,"name":"Paniz Rezvan Sangsari","orcid":null,"position":5,"is_corresponding":false},{"id":300742,"name":"Nicole Y. Morgan","orcid":"0000-0003-0849-188X","position":6,"is_corresponding":false},{"id":331664,"name":"Ryan Dale","orcid":"0000-0003-2664-3744","position":7,"is_corresponding":false},{"id":225567,"name":"Michael E. Ward","orcid":"0000-0002-5296-8051","position":8,"is_corresponding":false},{"id":62801,"name":"Juan S. Bonifacino","orcid":"0000-0002-5673-6370","position":9,"is_corresponding":false},{"id":86557,"name":"Raffaella De Pace","orcid":"0000-0002-8179-6869","position":0,"is_corresponding":true}],"reference_count":94,"raw_metadata":null,"created_at":"2026-07-19T01:56:50.743370Z","pmid":"38600167","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}