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Ltc1 is an ER-localized sterol transporter and a component of ER–mitochondria and ER–vacuole contacts
Organelle contact sites perform fundamental functions in cells, including lipid and ion homeostasis, membrane dynamics, and signaling. Using a forward proteomics approach in yeast, we identified new ER–mitochondria and ER–vacuole contacts specified by an uncharacterized protein, Ylr072w. Ylr072w is...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4442815/ https://www.ncbi.nlm.nih.gov/pubmed/25987606 http://dx.doi.org/10.1083/jcb.201502033 |
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author | Murley, Andrew Sarsam, Reta D. Toulmay, Alexandre Yamada, Justin Prinz, William A. Nunnari, Jodi |
author_facet | Murley, Andrew Sarsam, Reta D. Toulmay, Alexandre Yamada, Justin Prinz, William A. Nunnari, Jodi |
author_sort | Murley, Andrew |
collection | PubMed |
description | Organelle contact sites perform fundamental functions in cells, including lipid and ion homeostasis, membrane dynamics, and signaling. Using a forward proteomics approach in yeast, we identified new ER–mitochondria and ER–vacuole contacts specified by an uncharacterized protein, Ylr072w. Ylr072w is a conserved protein with GRAM and VASt domains that selectively transports sterols and is thus termed Ltc1, for Lipid transfer at contact site 1. Ltc1 localized to ER–mitochondria and ER–vacuole contacts via the mitochondrial import receptors Tom70/71 and the vacuolar protein Vac8, respectively. At mitochondria, Ltc1 was required for cell viability in the absence of Mdm34, a subunit of the ER–mitochondria encounter structure. At vacuoles, Ltc1 was required for sterol-enriched membrane domain formation in response to stress. Increasing the proportion of Ltc1 at vacuoles was sufficient to induce sterol-enriched vacuolar domains without stress. Thus, our data support a model in which Ltc1 is a sterol-dependent regulator of organelle and cellular homeostasis via its dual localization to ER–mitochondria and ER–vacuole contact sites. |
format | Online Article Text |
id | pubmed-4442815 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-44428152015-11-25 Ltc1 is an ER-localized sterol transporter and a component of ER–mitochondria and ER–vacuole contacts Murley, Andrew Sarsam, Reta D. Toulmay, Alexandre Yamada, Justin Prinz, William A. Nunnari, Jodi J Cell Biol Research Articles Organelle contact sites perform fundamental functions in cells, including lipid and ion homeostasis, membrane dynamics, and signaling. Using a forward proteomics approach in yeast, we identified new ER–mitochondria and ER–vacuole contacts specified by an uncharacterized protein, Ylr072w. Ylr072w is a conserved protein with GRAM and VASt domains that selectively transports sterols and is thus termed Ltc1, for Lipid transfer at contact site 1. Ltc1 localized to ER–mitochondria and ER–vacuole contacts via the mitochondrial import receptors Tom70/71 and the vacuolar protein Vac8, respectively. At mitochondria, Ltc1 was required for cell viability in the absence of Mdm34, a subunit of the ER–mitochondria encounter structure. At vacuoles, Ltc1 was required for sterol-enriched membrane domain formation in response to stress. Increasing the proportion of Ltc1 at vacuoles was sufficient to induce sterol-enriched vacuolar domains without stress. Thus, our data support a model in which Ltc1 is a sterol-dependent regulator of organelle and cellular homeostasis via its dual localization to ER–mitochondria and ER–vacuole contact sites. The Rockefeller University Press 2015-05-25 /pmc/articles/PMC4442815/ /pubmed/25987606 http://dx.doi.org/10.1083/jcb.201502033 Text en © 2015 Murley 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 Murley, Andrew Sarsam, Reta D. Toulmay, Alexandre Yamada, Justin Prinz, William A. Nunnari, Jodi Ltc1 is an ER-localized sterol transporter and a component of ER–mitochondria and ER–vacuole contacts |
title | Ltc1 is an ER-localized sterol transporter and a component of ER–mitochondria and ER–vacuole contacts |
title_full | Ltc1 is an ER-localized sterol transporter and a component of ER–mitochondria and ER–vacuole contacts |
title_fullStr | Ltc1 is an ER-localized sterol transporter and a component of ER–mitochondria and ER–vacuole contacts |
title_full_unstemmed | Ltc1 is an ER-localized sterol transporter and a component of ER–mitochondria and ER–vacuole contacts |
title_short | Ltc1 is an ER-localized sterol transporter and a component of ER–mitochondria and ER–vacuole contacts |
title_sort | ltc1 is an er-localized sterol transporter and a component of er–mitochondria and er–vacuole contacts |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4442815/ https://www.ncbi.nlm.nih.gov/pubmed/25987606 http://dx.doi.org/10.1083/jcb.201502033 |
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