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The FATP1–DGAT2 complex facilitates lipid droplet expansion at the ER–lipid droplet interface
At the subcellular level, fat storage is confined to the evolutionarily conserved compartments termed lipid droplets (LDs), which are closely associated with the endoplasmic reticulum (ER). However, the molecular mechanisms that enable ER–LD interaction and facilitate neutral lipid loading into LDs...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3432760/ https://www.ncbi.nlm.nih.gov/pubmed/22927462 http://dx.doi.org/10.1083/jcb.201201139 |
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author | Xu, Ningyi Zhang, Shaobing O. Cole, Ronald A. McKinney, Sean A. Guo, Fengli Haas, Joel T. Bobba, Sudheer Farese, Robert V. Mak, Ho Yi |
author_facet | Xu, Ningyi Zhang, Shaobing O. Cole, Ronald A. McKinney, Sean A. Guo, Fengli Haas, Joel T. Bobba, Sudheer Farese, Robert V. Mak, Ho Yi |
author_sort | Xu, Ningyi |
collection | PubMed |
description | At the subcellular level, fat storage is confined to the evolutionarily conserved compartments termed lipid droplets (LDs), which are closely associated with the endoplasmic reticulum (ER). However, the molecular mechanisms that enable ER–LD interaction and facilitate neutral lipid loading into LDs are poorly understood. In this paper, we present evidence that FATP1/acyl-CoA synthetase and DGAT2/diacylglycerol acyltransferase are components of a triglyceride synthesis complex that facilitates LD expansion. A loss of FATP1 or DGAT2 function blocked LD expansion in Caenorhabditis elegans. FATP1 preferentially associated with DGAT2, and they acted synergistically to promote LD expansion in mammalian cells. Live imaging indicated that FATP1 and DGAT2 are ER and LD resident proteins, respectively, and electron microscopy revealed FATP1 and DGAT2 foci close to the LD surface. Furthermore, DGAT2 that was retained in the ER failed to support LD expansion. We propose that the evolutionarily conserved FATP1–DGAT2 complex acts at the ER–LD interface and couples the synthesis and deposition of triglycerides into LDs both physically and functionally. |
format | Online Article Text |
id | pubmed-3432760 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-34327602013-03-03 The FATP1–DGAT2 complex facilitates lipid droplet expansion at the ER–lipid droplet interface Xu, Ningyi Zhang, Shaobing O. Cole, Ronald A. McKinney, Sean A. Guo, Fengli Haas, Joel T. Bobba, Sudheer Farese, Robert V. Mak, Ho Yi J Cell Biol Research Articles At the subcellular level, fat storage is confined to the evolutionarily conserved compartments termed lipid droplets (LDs), which are closely associated with the endoplasmic reticulum (ER). However, the molecular mechanisms that enable ER–LD interaction and facilitate neutral lipid loading into LDs are poorly understood. In this paper, we present evidence that FATP1/acyl-CoA synthetase and DGAT2/diacylglycerol acyltransferase are components of a triglyceride synthesis complex that facilitates LD expansion. A loss of FATP1 or DGAT2 function blocked LD expansion in Caenorhabditis elegans. FATP1 preferentially associated with DGAT2, and they acted synergistically to promote LD expansion in mammalian cells. Live imaging indicated that FATP1 and DGAT2 are ER and LD resident proteins, respectively, and electron microscopy revealed FATP1 and DGAT2 foci close to the LD surface. Furthermore, DGAT2 that was retained in the ER failed to support LD expansion. We propose that the evolutionarily conserved FATP1–DGAT2 complex acts at the ER–LD interface and couples the synthesis and deposition of triglycerides into LDs both physically and functionally. The Rockefeller University Press 2012-09-03 /pmc/articles/PMC3432760/ /pubmed/22927462 http://dx.doi.org/10.1083/jcb.201201139 Text en © 2012 Xu et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles Xu, Ningyi Zhang, Shaobing O. Cole, Ronald A. McKinney, Sean A. Guo, Fengli Haas, Joel T. Bobba, Sudheer Farese, Robert V. Mak, Ho Yi The FATP1–DGAT2 complex facilitates lipid droplet expansion at the ER–lipid droplet interface |
title | The FATP1–DGAT2 complex facilitates lipid droplet expansion at the ER–lipid droplet interface |
title_full | The FATP1–DGAT2 complex facilitates lipid droplet expansion at the ER–lipid droplet interface |
title_fullStr | The FATP1–DGAT2 complex facilitates lipid droplet expansion at the ER–lipid droplet interface |
title_full_unstemmed | The FATP1–DGAT2 complex facilitates lipid droplet expansion at the ER–lipid droplet interface |
title_short | The FATP1–DGAT2 complex facilitates lipid droplet expansion at the ER–lipid droplet interface |
title_sort | fatp1–dgat2 complex facilitates lipid droplet expansion at the er–lipid droplet interface |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3432760/ https://www.ncbi.nlm.nih.gov/pubmed/22927462 http://dx.doi.org/10.1083/jcb.201201139 |
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