Ltc1 is an ER-localized sterol transporter and a component of ER-mitochondria and ER-vacuole contacts

Andrew Murley, Reta D. Sarsam, Alexandre Toulmay, Justin Yamada, William A. Prinz, Jodi Nunnari

Research output: Contribution to journalArticle

127 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)539-548
Number of pages10
JournalJournal of Cell Biology
Volume209
Issue number4
DOIs
StatePublished - 2015

ASJC Scopus subject areas

  • Cell Biology
  • Medicine(all)

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    Murley, A., Sarsam, R. D., Toulmay, A., Yamada, J., Prinz, W. A., & Nunnari, J. (2015). Ltc1 is an ER-localized sterol transporter and a component of ER-mitochondria and ER-vacuole contacts. Journal of Cell Biology, 209(4), 539-548. https://doi.org/10.1083/jcb.201502033