PI(3)P and DFCP1 regulate the biogenesis of lipid droplets
The biogenesis of lipid droplets (LDs), key organelles for cellular lipid storage and homeostasis, remains poorly understood. Seipin is essential to normal LD biogenesis but exactly how it regulates LD initiation remains to be elucidated. Our previous results suggested that seipin may bind anionic p...
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| Veröffentlicht in: | Molecular biology of the cell 2022-12, Vol.33 (14), p.ar131-ar131 |
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| container_title | Molecular biology of the cell |
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| creator | Lukmantara, Ivan Chen, Fang Mak, Hoi Yin Zadoorian, Armella Du, Ximing Xiao, Fanqian Nicole Norris, Dougall MacMurray Pandzic, Elvis Whan, Renee Zhong, Qing Yang, Hongyuan |
| description | The biogenesis of lipid droplets (LDs), key organelles for cellular lipid storage and homeostasis, remains poorly understood. Seipin is essential to normal LD biogenesis but exactly how it regulates LD initiation remains to be elucidated. Our previous results suggested that seipin may bind anionic phospholipids such as PI(3)P. Here, we investigate whether PI(3)P is functionally linked to seipin and whether PI(3)P can also impact LD biogenesis. In seipin-deficient cells, there were enlarged PI(3)P puncta where its effector, DFCP1, also appeared to congregate. Reducing cellular PI(3)P partially rescued the defective LD initiation caused by seipin deficiency. Increasing PI(3)P impeded the lipidation of nascent LDs. We further demonstrated that DFCP1 localized to LDs and facilitated the efficient lipidation of nascent LDs. However, the normal function and localization of DFCP1 were disrupted when cellular PI(3)P homeostasis was perturbed. Our results thus identify PI(3)P as a novel regulator of LD initiation and suggest that PI(3)P may impact the biogenesis of LDs through DFCP1. |
| doi_str_mv | 10.1091/mbc.E22-07-0279 |
| format | Article |
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Seipin is essential to normal LD biogenesis but exactly how it regulates LD initiation remains to be elucidated. Our previous results suggested that seipin may bind anionic phospholipids such as PI(3)P. Here, we investigate whether PI(3)P is functionally linked to seipin and whether PI(3)P can also impact LD biogenesis. In seipin-deficient cells, there were enlarged PI(3)P puncta where its effector, DFCP1, also appeared to congregate. Reducing cellular PI(3)P partially rescued the defective LD initiation caused by seipin deficiency. Increasing PI(3)P impeded the lipidation of nascent LDs. We further demonstrated that DFCP1 localized to LDs and facilitated the efficient lipidation of nascent LDs. However, the normal function and localization of DFCP1 were disrupted when cellular PI(3)P homeostasis was perturbed. Our results thus identify PI(3)P as a novel regulator of LD initiation and suggest that PI(3)P may impact the biogenesis of LDs through DFCP1.</description><identifier>ISSN: 1059-1524</identifier><identifier>EISSN: 1939-4586</identifier><identifier>DOI: 10.1091/mbc.E22-07-0279</identifier><identifier>PMID: 36129766</identifier><language>eng</language><publisher>United States: The American Society for Cell Biology</publisher><subject>Lipid Droplets - metabolism ; Lipid Metabolism ; Phospholipids - metabolism</subject><ispartof>Molecular biology of the cell, 2022-12, Vol.33 (14), p.ar131-ar131</ispartof><rights>2022 Lukmantara, Chen, Mak, Zadoorian, “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. 2022</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c393t-170b1ca64dded340d6ef1700ce69ddd9466d945f26be72d6f99ad6998db0763f3</citedby><cites>FETCH-LOGICAL-c393t-170b1ca64dded340d6ef1700ce69ddd9466d945f26be72d6f99ad6998db0763f3</cites><orcidid>0000-0002-8482-6031</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9727793/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9727793/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36129766$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lukmantara, Ivan</creatorcontrib><creatorcontrib>Chen, Fang</creatorcontrib><creatorcontrib>Mak, Hoi Yin</creatorcontrib><creatorcontrib>Zadoorian, Armella</creatorcontrib><creatorcontrib>Du, Ximing</creatorcontrib><creatorcontrib>Xiao, Fanqian Nicole</creatorcontrib><creatorcontrib>Norris, Dougall MacMurray</creatorcontrib><creatorcontrib>Pandzic, Elvis</creatorcontrib><creatorcontrib>Whan, Renee</creatorcontrib><creatorcontrib>Zhong, Qing</creatorcontrib><creatorcontrib>Yang, Hongyuan</creatorcontrib><title>PI(3)P and DFCP1 regulate the biogenesis of lipid droplets</title><title>Molecular biology of the cell</title><addtitle>Mol Biol Cell</addtitle><description>The biogenesis of lipid droplets (LDs), key organelles for cellular lipid storage and homeostasis, remains poorly understood. Seipin is essential to normal LD biogenesis but exactly how it regulates LD initiation remains to be elucidated. Our previous results suggested that seipin may bind anionic phospholipids such as PI(3)P. Here, we investigate whether PI(3)P is functionally linked to seipin and whether PI(3)P can also impact LD biogenesis. In seipin-deficient cells, there were enlarged PI(3)P puncta where its effector, DFCP1, also appeared to congregate. Reducing cellular PI(3)P partially rescued the defective LD initiation caused by seipin deficiency. Increasing PI(3)P impeded the lipidation of nascent LDs. We further demonstrated that DFCP1 localized to LDs and facilitated the efficient lipidation of nascent LDs. However, the normal function and localization of DFCP1 were disrupted when cellular PI(3)P homeostasis was perturbed. Our results thus identify PI(3)P as a novel regulator of LD initiation and suggest that PI(3)P may impact the biogenesis of LDs through DFCP1.</description><subject>Lipid Droplets - metabolism</subject><subject>Lipid Metabolism</subject><subject>Phospholipids - metabolism</subject><issn>1059-1524</issn><issn>1939-4586</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkE1PwzAMhiMEYmNw5oZyHIeOfLTJwgEJjQ0mTWIHOEdp425B_SJpkfj3dNqY4GJb9uvX1oPQNSUTShS9K9NsMmcsIjIiTKoTNKSKqyhOpuK0r0miIpqweIAuQvgghMaxkOdowAVlSgoxRPfr5ZjfrrGpLH5azNYUe9h0hWkBt1vAqas3UEFwAdc5LlzjLLa-bgpowyU6y00R4OqQR-h9MX-bvUSr1-fl7HEVZVzxNqKSpDQzIrYWLI-JFZD3PZKBUNZaFQvRhyRnIgXJrMiVMlYoNbUpkYLnfIQe9r5Nl5ZgM6habwrdeFca_61r4_T_SeW2elN_aSWZlIr3BuODga8_OwitLl3IoChMBXUXNJNUJCxR06SX3u2lma9D8JAfz1Cid8R1T1z3xDWReke837j5-91R_4uY_wBE4nwv</recordid><startdate>20221201</startdate><enddate>20221201</enddate><creator>Lukmantara, Ivan</creator><creator>Chen, Fang</creator><creator>Mak, Hoi Yin</creator><creator>Zadoorian, Armella</creator><creator>Du, Ximing</creator><creator>Xiao, Fanqian Nicole</creator><creator>Norris, Dougall MacMurray</creator><creator>Pandzic, Elvis</creator><creator>Whan, Renee</creator><creator>Zhong, Qing</creator><creator>Yang, Hongyuan</creator><general>The American Society for Cell Biology</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-8482-6031</orcidid></search><sort><creationdate>20221201</creationdate><title>PI(3)P and DFCP1 regulate the biogenesis of lipid droplets</title><author>Lukmantara, Ivan ; Chen, Fang ; Mak, Hoi Yin ; Zadoorian, Armella ; Du, Ximing ; Xiao, Fanqian Nicole ; Norris, Dougall MacMurray ; Pandzic, Elvis ; Whan, Renee ; Zhong, Qing ; Yang, Hongyuan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c393t-170b1ca64dded340d6ef1700ce69ddd9466d945f26be72d6f99ad6998db0763f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Lipid Droplets - metabolism</topic><topic>Lipid Metabolism</topic><topic>Phospholipids - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lukmantara, Ivan</creatorcontrib><creatorcontrib>Chen, Fang</creatorcontrib><creatorcontrib>Mak, Hoi Yin</creatorcontrib><creatorcontrib>Zadoorian, Armella</creatorcontrib><creatorcontrib>Du, Ximing</creatorcontrib><creatorcontrib>Xiao, Fanqian Nicole</creatorcontrib><creatorcontrib>Norris, Dougall MacMurray</creatorcontrib><creatorcontrib>Pandzic, Elvis</creatorcontrib><creatorcontrib>Whan, Renee</creatorcontrib><creatorcontrib>Zhong, Qing</creatorcontrib><creatorcontrib>Yang, Hongyuan</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Molecular biology of the cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lukmantara, Ivan</au><au>Chen, Fang</au><au>Mak, Hoi Yin</au><au>Zadoorian, Armella</au><au>Du, Ximing</au><au>Xiao, Fanqian Nicole</au><au>Norris, Dougall MacMurray</au><au>Pandzic, Elvis</au><au>Whan, Renee</au><au>Zhong, Qing</au><au>Yang, Hongyuan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>PI(3)P and DFCP1 regulate the biogenesis of lipid droplets</atitle><jtitle>Molecular biology of the cell</jtitle><addtitle>Mol Biol Cell</addtitle><date>2022-12-01</date><risdate>2022</risdate><volume>33</volume><issue>14</issue><spage>ar131</spage><epage>ar131</epage><pages>ar131-ar131</pages><issn>1059-1524</issn><eissn>1939-4586</eissn><abstract>The biogenesis of lipid droplets (LDs), key organelles for cellular lipid storage and homeostasis, remains poorly understood. Seipin is essential to normal LD biogenesis but exactly how it regulates LD initiation remains to be elucidated. Our previous results suggested that seipin may bind anionic phospholipids such as PI(3)P. Here, we investigate whether PI(3)P is functionally linked to seipin and whether PI(3)P can also impact LD biogenesis. In seipin-deficient cells, there were enlarged PI(3)P puncta where its effector, DFCP1, also appeared to congregate. Reducing cellular PI(3)P partially rescued the defective LD initiation caused by seipin deficiency. Increasing PI(3)P impeded the lipidation of nascent LDs. We further demonstrated that DFCP1 localized to LDs and facilitated the efficient lipidation of nascent LDs. However, the normal function and localization of DFCP1 were disrupted when cellular PI(3)P homeostasis was perturbed. 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| subjects | Lipid Droplets - metabolism Lipid Metabolism Phospholipids - metabolism |
| title | PI(3)P and DFCP1 regulate the biogenesis of lipid droplets |
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