{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Lie PPY"],"funding":["NIA NIH HHS"],"pagination":["eabj5716"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9054012"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["8(17)"],"pubmed_abstract":["Dysfunction and mistrafficking of organelles in autophagy- and endosomal-lysosomal pathways are implicated in neurodegenerative diseases. Here, we reveal selective vulnerability of maturing degradative organelles (late endosomes/amphisomes) to disease-relevant local calcium dysregulation. These organelles undergo exclusive retrograde transport in axons, with occasional pauses triggered by regulated calcium efflux from agonist-evoked transient receptor potential cation channel mucolipin subfamily member 1 (TRPML1) channels-an effect greatly exaggerated by exogenous agonist mucolipin synthetic agonist 1 (ML-SA1). Deacidification of degradative organelles, as seen after Presenilin 1 (PSEN1) loss of function, induced pathological constitutive \"inside-out\" TRPML1 hyperactivation, slowing their "],"journal":["Science advances"],"pubmed_title":["Axonal transport of late endosomes and amphisomes is selectively modulated by local Ca<sup>2+</sup> efflux and disrupted by PSEN1 loss of function."],"pmcid":["PMC9054012"],"funding_grant_id":["R01 AG062376"],"pubmed_authors":["Lie PPY","Huo C","Goulbourne CN","Stavrides P","Nixon RA","Yoo L","Berg MJ","Lee JH"],"additional_accession":[]},"is_claimable":false,"name":"Axonal transport of late endosomes and amphisomes is selectively modulated by local Ca<sup>2+</sup> efflux and disrupted by PSEN1 loss of function.","description":"Dysfunction and mistrafficking of organelles in autophagy- and endosomal-lysosomal pathways are implicated in neurodegenerative diseases. Here, we reveal selective vulnerability of maturing degradative organelles (late endosomes/amphisomes) to disease-relevant local calcium dysregulation. These organelles undergo exclusive retrograde transport in axons, with occasional pauses triggered by regulated calcium efflux from agonist-evoked transient receptor potential cation channel mucolipin subfamily member 1 (TRPML1) channels-an effect greatly exaggerated by exogenous agonist mucolipin synthetic agonist 1 (ML-SA1). Deacidification of degradative organelles, as seen after Presenilin 1 (PSEN1) loss of function, induced pathological constitutive \"inside-out\" TRPML1 hyperactivation, slowing their ","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Apr","modification":"2025-04-19T09:20:06.664Z","creation":"2025-04-19T09:20:06.664Z"},"accession":"S-EPMC9054012","cross_references":{"pubmed":["35486730"],"doi":["10.1126/sciadv.abj5716"]}}