{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:58:09Z","timestamp":1792789089986,"version":"4.5.0"},"reference-count":36,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32470080"],"award-info":[{"award-number":["32470080"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["32470080"],"award-info":[{"award-number":["32470080"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Northwest A&F University Start-up Funding","award":["A2190022006"],"award-info":[{"award-number":["A2190022006"]}],"id":[{"id":"https:\/\/ror.org\/0051rme32","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Lipid droplets are dynamic organelles that store neutral lipids (mostly triacylglycerols and sterol esters) and are bound by a single phospholipid monolayer. The formation and breakdown of the droplets are important for cellular metabolism; however, the molecular mechanisms regulating their biogenesis and turnover are still obscure. In this study, we used Erg6-yeGFP as a lipid droplet marker, isolated 1100 temperature-sensitive mutants, and observed lipid droplet morphology in these mutants by fluorescence microscopy. Six mutants with abnormal lipid droplet morphology were obtained and next-generation sequencing identified responsible mutations in genes encoding subunits of HOPS complex or its binding partner Ypt7. Therefore, the genetic screen indicated that the HOPS complex plays a critical role in maintaining lipid droplet morphology. In the absence of Vps11, vacuoles were fragmented with dot-like structures and degradation of lipid droplet surface protein Erg6 (under glucose starvation condition) decreased dramatically. A genetic screen for mutations that could rescue the abnormal lipid droplet morphology in \u0394vps11 by fluorescence microscopy identified two independent mutations in vps1302. Vps1301 and Vps1302 are paralogs that function as intermembrane lipid transfer proteins. Deletion of either vps1301 or vps1302 rescued the abnormal lipid droplet morphology in \u0394vps11 as well.<\/jats:p>","DOI":"10.3390\/cells15191724","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T11:09:35Z","timestamp":1790075375000},"page":"1724","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["HOPS and Vps13 Have Antagonistic Roles in Regulating Lipid Droplet Morphology"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-9537-0097","authenticated-orcid":false,"given":"Jie","family":"Wang","sequence":"first","affiliation":[{"name":"Institute of Future Agriculture, Northwest A&F University, Yangling 712100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saidaiguli","family":"Abulimiti","sequence":"additional","affiliation":[{"name":"Institute of Future Agriculture, Northwest A&F University, Yangling 712100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingping","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Future Agriculture, Northwest A&F University, Yangling 712100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinping","family":"Zheng","sequence":"additional","affiliation":[{"name":"Institute of Future Agriculture, Northwest A&F University, Yangling 712100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanjing","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Future Agriculture, Northwest A&F University, Yangling 712100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Lei","sequence":"additional","affiliation":[{"name":"Institute of Future Agriculture, Northwest A&F University, Yangling 712100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingya","family":"Xu","sequence":"additional","affiliation":[{"name":"Institute of Future Agriculture, Northwest A&F University, Yangling 712100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1146\/annurev-biochem-061009-102430","article-title":"Lipid droplets and cellular lipid metabolism","volume":"81","author":"Walther","year":"2012","journal-title":"Annu. Rev. Biochem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.ceb.2012.05.012","article-title":"Controlling the size of lipid droplets: Lipid and protein factors","volume":"24","author":"Yang","year":"2012","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1038\/s41580-018-0085-z","article-title":"Dynamics and functions of lipid droplets","volume":"20","author":"Olzmann","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1038\/nature07976","article-title":"Autophagy regulates lipid metabolism","volume":"458","author":"Singh","year":"2009","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1091\/mbc.e13-08-0448","article-title":"Lipid droplet autophagy in the yeast Saccharomyces cerevisiae","volume":"25","author":"Todde","year":"2014","journal-title":"Mol. Biol. Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1002\/yea.3705","article-title":"Lipophagy pathways in yeast are controlled by their distinct modes of induction","volume":"39","author":"Fairman","year":"2022","journal-title":"Yeast"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1111\/tra.12732","article-title":"The endosomal sorting complex required for transport complex negatively regulates Erg6 degradation under specific glucose restriction conditions","volume":"21","author":"Zhang","year":"2020","journal-title":"Traffic"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1242\/jcs.107805","article-title":"CORVET and HOPS tethering complexes\u2014Coordinators of endosome and lysosome fusion","volume":"126","author":"Balderhaar","year":"2013","journal-title":"J. Cell Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1091\/mbc.e13-08-0447","article-title":"The HOPS complex mediates autophagosome-lysosome fusion through interaction with syntaxin 17","volume":"25","author":"Jiang","year":"2014","journal-title":"Mol. Biol. Cell"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/164_2023_640","article-title":"Lysosomal Ion Channels and Lysosome-Organelle Interactions","volume":"278","author":"Cai","year":"2023","journal-title":"Handb. Exp. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/j.ceb.2009.05.007","article-title":"Vps-C complexes: Gatekeepers of endolysosomal traffic","volume":"21","author":"Nickerson","year":"2009","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1242\/bio.20148615","article-title":"Regulation of lipid droplet dynamics in Saccharomyces cerevisiae depends on the Rab7-like Ypt7p, HOPS complex and V1-ATPase","volume":"4","author":"Bouchez","year":"2015","journal-title":"Biol. Open"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Konig, C., Shvarev, D., Gao, J., Haar, E., Susan, N., Auffarth, K., Langemeyer, L., Moeller, A., and Ungermann, C. (2025). Vps41 functions as a molecular ruler for HOPS tethering complex-mediated membrane fusion. J. Cell Sci., 138.","DOI":"10.1242\/jcs.263788"},{"key":"ref_14","first-page":"25152564221125613","article-title":"VPS13A and VPS13C Influence Lipid Droplet Abundance","volume":"5","author":"Chen","year":"2022","journal-title":"Contact"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Dziurdzik, S.K., and Conibear, E. (2021). The Vps13 Family of Lipid Transporters and Its Role at Membrane Contact Sites. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22062905"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"159003","DOI":"10.1016\/j.bbalip.2021.159003","article-title":"Insights into VPS13 properties and function reveal a new mechanism of eukaryotic lipid transport","volume":"1866","author":"Leonzino","year":"2021","journal-title":"Biochim. Biophys. Acta Mol. Cell. Biol. Lipids"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"E4833","DOI":"10.1073\/pnas.1803564115","article-title":"Suppressor mutation analysis combined with 3D modeling explains cohesin\u2019s capacity to hold and release DNA","volume":"115","author":"Xu","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e2208004119","DOI":"10.1073\/pnas.2208004119","article-title":"Cohesin ATPase activities regulate DNA binding and coiled-coil configuration","volume":"119","author":"Xu","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"10889","DOI":"10.1073\/pnas.1902699116","article-title":"Suppressor screening reveals common kleisin-hinge interaction in condensin and cohesin, but different modes of regulation","volume":"116","author":"Xu","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1038\/s41580-025-00945-x","article-title":"Heterogeneity, dynamics and organelle interactions of lipid droplets","volume":"27","author":"Henne","year":"2026","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1194\/jlr.R024117","article-title":"The proteomics of lipid droplets: Structure, dynamics, and functions of the organelle conserved from bacteria to humans","volume":"53","author":"Yang","year":"2012","journal-title":"J. Lipid Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1007\/s12275-017-6205-1","article-title":"The protein and neutral lipid composition of lipid droplets isolated from the fission yeast, Schizosaccharomyces pombe","volume":"55","author":"Meyers","year":"2017","journal-title":"J. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Zou, C.X., Ma, Z.H., Jiang, Z.D., Pan, Z.Q., Xu, D.D., Suo, F., Shao, G.C., Dong, M.Q., and Du, L.L. (2023). The ortholog of human REEP1-4 is required for autophagosomal enclosure of ER-phagy\/nucleophagy cargos in fission yeast. PLoS Biol., 21.","DOI":"10.1101\/2023.04.24.538066"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2743","DOI":"10.1111\/febs.12151","article-title":"Tethering complexes in the endocytic pathway: CORVET and HOPS","volume":"280","author":"Solinger","year":"2013","journal-title":"FEBS J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1002\/yea.1134","article-title":"Characterization of end4+, a gene required for endocytosis in Schizosaccharomyces pombe","volume":"21","author":"Iwaki","year":"2004","journal-title":"Yeast"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.1242\/jcs.046466","article-title":"Genetic control of cellular quiescence in S. pombe","volume":"122","author":"Sajiki","year":"2009","journal-title":"J. Cell Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1242\/jcs.196352","article-title":"New insights into autophagosome-lysosome fusion","volume":"130","author":"Nakamura","year":"2017","journal-title":"J. Cell Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1080\/15548627.2024.2325297","article-title":"General autophagy-dependent and -independent lipophagic processes collaborate to regulate the overall level of lipophagy in yeast","volume":"20","author":"Kang","year":"2024","journal-title":"Autophagy"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Kumar, R., Rahman, M.A., and Nazarko, T.Y. (2020). Nitrogen Starvation and Stationary Phase Lipophagy Have Distinct Molecular Mechanisms. Int. J. Mol. Sci., 21.","DOI":"10.1101\/2020.03.17.996082"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1016\/j.molcel.2015.07.034","article-title":"ESCRTs Cooperate with a Selective Autophagy Receptor to Mediate Vacuolar Targeting of Soluble Cargos","volume":"59","author":"Liu","year":"2015","journal-title":"Mol. Cell"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1016\/j.cmet.2008.09.004","article-title":"Insig regulates HMG-CoA reductase by controlling enzyme phosphorylation in fission yeast","volume":"8","author":"Burg","year":"2008","journal-title":"Cell Metab."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"108777","DOI":"10.1016\/j.isci.2023.108777","article-title":"Rapamycin-sensitive mechanisms confine the growth of fission yeast below the temperatures detrimental to cell physiology","volume":"27","author":"Morozumi","year":"2024","journal-title":"iScience"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4035","DOI":"10.1093\/emboj\/20.15.4035","article-title":"Ergosterol is required for the Sec18\/ATP-dependent priming step of homotypic vacuole fusion","volume":"20","author":"Kato","year":"2001","journal-title":"EMBO J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1083\/jcb.201301039","article-title":"Direct imaging reveals stable, micrometer-scale lipid domains that segregate proteins in live cells","volume":"202","author":"Toulmay","year":"2013","journal-title":"J. Cell Biol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Park, J.S., Hollingsworth, N.M., and Neiman, A.M. (2021). Genetic Dissection of Vps13 Regulation in Yeast Using Disease Mutations from Human Orthologs. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22126200"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1534\/genetics.115.181503","article-title":"An Ancient Yeast for Young Geneticists: A Primer on the Schizosaccharomyces pombe Model System","volume":"201","author":"Hoffman","year":"2015","journal-title":"Genetics"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/19\/1724\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T11:15:21Z","timestamp":1790075721000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/19\/1724"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,22]]},"references-count":36,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["cells15191724"],"URL":"https:\/\/doi.org\/10.3390\/cells15191724","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,22]]}}}