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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...

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Autores principales: Murley, Andrew, Sarsam, Reta D., Toulmay, Alexandre, Yamada, Justin, Prinz, William A., Nunnari, Jodi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2015
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.
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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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