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A proper assembly of TAG-containing LDs at the ER requires Seipin, a conserved protein often mutated in lipodystrophies. Here, we show that the yeast Seipin Sei1 and its partner Ldb16 also promote the storage of other NL in LDs. Importantly, this role of Sei1\/Ldb16 is evolutionarily conserved as expression of human-Seipin restored normal SE-containing LDs in yeast Seipin mutants. As in the case of TAG, the formation of SE-containing LDs requires interactions between hydroxyl-residues in human Seipin or yeast Ldb16 with NL carboxyl esters. These findings provide a universal mechanism for Seipin-mediated LD formation and suggest a model for how Seipin distinguishes NLs from aliphatic phospholipid acyl chains in the center of the membrane bilayer.<\/jats:p>","DOI":"10.1083\/jcb.202112068","type":"journal-article","created":{"date-parts":[[2023,4,26]],"date-time":"2023-04-26T14:10:04Z","timestamp":1682518204000},"update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":36,"title":["Seipin concentrates distinct neutral lipids via interactions with their acyl chain carboxyl esters"],"prefix":"10.1083","volume":"221","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0508-2298","authenticated-orcid":true,"given":"Mike F.","family":"Renne","sequence":"first","affiliation":[{"name":"Sir William Dunn School of Pathology, University of Oxford, Oxford, UK 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1820-7993","authenticated-orcid":true,"given":"Robin A.","family":"Corey","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Oxford, Oxford, UK 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4341-1654","authenticated-orcid":true,"given":"Joana Ver\u00edssimo","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Sir William Dunn School of Pathology, University of Oxford, Oxford, UK 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8800-7669","authenticated-orcid":true,"given":"Phillip J.","family":"Stansfeld","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Oxford, Oxford, UK 2"},{"name":"School of Life Sciences and Department of Chemistry, University of Warwick, Coventry, UK 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9691-5277","authenticated-orcid":true,"given":"Pedro","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Sir William Dunn School of Pathology, University of Oxford, Oxford, UK 1"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2022,8,8]]},"reference":[{"key":"2023080923054171300_bib1","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.softx.2015.06.001","article-title":"GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers","volume":"1\u20132","author":"Abraham","year":"2015","journal-title":"SoftwareX"},{"key":"2023080923054171300_bib2","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1083\/jcb.201010111","article-title":"The yeast lipin orthologue Pah1p is important for biogenesis of lipid droplets","volume":"192","author":"Adeyo","year":"2011","journal-title":"J. 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