{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1362825894092457984.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1242/jcs.213587"}},{"identifier":{"@type":"URI","@value":"https://syndication.highwire.org/content/doi/10.1242/jcs.213587"}},{"identifier":{"@type":"URI","@value":"https://journals.biologists.com/jcs/article-pdf/doi/10.1242/jcs.213587/3514901/jcs213587.pdf"}},{"identifier":{"@type":"URI","@value":"http://journals.biologists.com/jcs/article-pdf/doi/10.1242/jcs.213587/2058754/jcs_213587v1.pdf"}}],"dc:title":[{"@value":"Lysosome enlargement during inhibition of the lipid kinase PIKfyve proceeds through lysosome coalescence"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:title>ABSTRACT</jats:title>\n                  <jats:p>Lysosomes receive and degrade cargo from endocytosis, phagocytosis and autophagy. They also play an important role in sensing and instructing cells on their metabolic state. The lipid kinase PIKfyve generates phosphatidylinositol-3,5-bisphosphate to modulate lysosome function. PIKfyve inhibition leads to impaired degradative capacity, ion dysregulation, abated autophagic flux and a massive enlargement of lysosomes. Collectively, this leads to various physiological defects, including embryonic lethality, neurodegeneration and overt inflammation. The reasons for such drastic lysosome enlargement remain unclear. Here, we examined whether biosynthesis and/or fusion-fission dynamics contribute to swelling. First, we show that PIKfyve inhibition activates TFEB, TFE3 and MITF, enhancing lysosome gene expression. However, this did not augment lysosomal protein levels during acute PIKfyve inhibition, and deletion of TFEB and/or related proteins did not impair lysosome swelling. Instead, PIKfyve inhibition led to fewer but enlarged lysosomes, suggesting that an imbalance favouring lysosome fusion over fission causes lysosome enlargement. Indeed, conditions that abated fusion curtailed lysosome swelling in PIKfyve-inhibited cells.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1382825894092457991","@type":"Researcher","foaf:name":[{"@value":"Christopher H. Choy"}],"jpcoar:affiliationName":[{"@value":"Ryerson University 1 Department of Chemistry and Biology , , Toronto, ON , Canada , M5B2K3"},{"@value":"Ryerson University 2 The Graduate Program in Molecular Science , , Toronto, ON , Canada , M5B2K3"}]},{"@id":"https://cir.nii.ac.jp/crid/1382825894092457989","@type":"Researcher","foaf:name":[{"@value":"Golam Saffi"}],"jpcoar:affiliationName":[{"@value":"Ryerson University 1 Department of Chemistry and Biology , , Toronto, ON , Canada , M5B2K3"},{"@value":"Ryerson University 2 The Graduate Program in Molecular Science , , Toronto, ON , Canada , M5B2K3"}]},{"@id":"https://cir.nii.ac.jp/crid/1382825894092457988","@type":"Researcher","foaf:name":[{"@value":"Matthew A. Gray"}],"jpcoar:affiliationName":[{"@value":"Ryerson University 1 Department of Chemistry and Biology , , Toronto, ON , Canada , M5B2K3"}]},{"@id":"https://cir.nii.ac.jp/crid/1382825894092457993","@type":"Researcher","foaf:name":[{"@value":"Callen Wallace"}],"jpcoar:affiliationName":[{"@value":"University of Pittsburgh 3 Department of Cell Biology , , Pittsburgh, PA 15261 , USA"}]},{"@id":"https://cir.nii.ac.jp/crid/1382825894092457987","@type":"Researcher","foaf:name":[{"@value":"Roya M. Dayam"}],"jpcoar:affiliationName":[{"@value":"Ryerson University 1 Department of Chemistry and Biology , , Toronto, ON , Canada , M5B2K3"},{"@value":"Ryerson University 2 The Graduate Program in Molecular Science , , Toronto, ON , Canada , M5B2K3"}]},{"@id":"https://cir.nii.ac.jp/crid/1382825894092457986","@type":"Researcher","foaf:name":[{"@value":"Zhen-Yi A. Ou"}],"jpcoar:affiliationName":[{"@value":"Ryerson University 1 Department of Chemistry and Biology , , Toronto, ON , Canada , M5B2K3"}]},{"@id":"https://cir.nii.ac.jp/crid/1382825894092457992","@type":"Researcher","foaf:name":[{"@value":"Guy Lenk"}],"jpcoar:affiliationName":[{"@value":"University of Michigan 4 Department of Human Genetics , , Ann Arbor, MI 48109 , USA"}]},{"@id":"https://cir.nii.ac.jp/crid/1382825894092457984","@type":"Researcher","foaf:name":[{"@value":"Rosa Puertollano"}],"jpcoar:affiliationName":[{"@value":"Cell Biology and Physiology Center, National Heart, Lung, and Blood Institute, National Institutes of Health 5 , 50 South Drive, Building 50, Room 3537, Bethesda, MD 20892 , USA"}]},{"@id":"https://cir.nii.ac.jp/crid/1382825894092457985","@type":"Researcher","foaf:name":[{"@value":"Simon C. Watkins"}],"jpcoar:affiliationName":[{"@value":"University of Pittsburgh 3 Department of Cell Biology , , Pittsburgh, PA 15261 , USA"}]},{"@id":"https://cir.nii.ac.jp/crid/1382825894092457990","@type":"Researcher","foaf:name":[{"@value":"Roberto J. Botelho"}],"jpcoar:affiliationName":[{"@value":"Ryerson University 1 Department of Chemistry and Biology , , Toronto, ON , Canada , M5B2K3"},{"@value":"Ryerson University 2 The Graduate Program in Molecular Science , , Toronto, ON , Canada , M5B2K3"}]}],"publication":{"publicationIdentifier":[{"@type":"EISSN","@value":"14779137"},{"@type":"PISSN","@value":"00219533"}],"prism:publicationName":[{"@value":"Journal of Cell Science"}],"dc:publisher":[{"@value":"The Company of Biologists"}],"prism:publicationDate":"2018-05-15","prism:volume":"131","prism:number":"10","prism:startingPage":"jcs213587"},"reviewed":"false","dc:rights":["http://www.biologists.com/user-licence-1-1/"],"url":[{"@id":"https://syndication.highwire.org/content/doi/10.1242/jcs.213587"},{"@id":"https://journals.biologists.com/jcs/article-pdf/doi/10.1242/jcs.213587/3514901/jcs213587.pdf"},{"@id":"http://journals.biologists.com/jcs/article-pdf/doi/10.1242/jcs.213587/2058754/jcs_213587v1.pdf"}],"createdAt":"2018-04-16","modifiedAt":"2024-06-13","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360013168832970240","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"PP2A-dependent TFEB activation is blocked by PIKfyve-induced mTORC1 activity"}]},{"@id":"https://cir.nii.ac.jp/crid/1360588380136769920","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"PIKFYVE inhibition induces endosome- and lysosome-derived vacuole enlargement via ammonium accumulation"}]},{"@id":"https://cir.nii.ac.jp/crid/1360861705558085248","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Abemaciclib and Vacuolin-1 induce vacuole-like autolysosome formation – A new tool to study autophagosome-lysosome fusion"}]},{"@id":"https://cir.nii.ac.jp/crid/1360865815693143936","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Abemaciclib and Vacuolin-1 decrease aggregate-prone TDP-43 accumulation by accelerating autophagic flux"}]},{"@id":"https://cir.nii.ac.jp/crid/1361694369417563904","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"PIKfyve accelerates phagosome acidification through activation of TRPML1 while arrests aberrant vacuolation independent of the Ca2+ channel"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.1242/jcs.213587"},{"@type":"CROSSREF","@value":"10.1091/mbc.e21-06-0309_references_DOI_3GPcH1LD1rhTQ4LOTkxD530ROSC"},{"@type":"CROSSREF","@value":"10.1016/j.bbrc.2022.05.027_references_DOI_3GPcH1LD1rhTQ4LOTkxD530ROSC"},{"@type":"CROSSREF","@value":"10.1242/jcs.262236_references_DOI_3GPcH1LD1rhTQ4LOTkxD530ROSC"},{"@type":"CROSSREF","@value":"10.1016/j.bbrep.2024.101705_references_DOI_3GPcH1LD1rhTQ4LOTkxD530ROSC"},{"@type":"CROSSREF","@value":"10.1093/jb/mvy084_references_DOI_3GPcH1LD1rhTQ4LOTkxD530ROSC"}]}