title: Ltc1 is an ER-localized sterol transporter and a component of ER-mitochondria and ER-vacuole contacts.
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.
authors.affiliation: Department of Molecular and Cellular Biology, University of California, Davis, Davis, CA 95616.
authors.forename: Andrew
authors.initials: A
authors.lastname: Murley
authors.affiliation: Department of Molecular and Cellular Biology, University of California, Davis, Davis, CA 95616.
authors.forename: Reta D
authors.initials: RD
authors.lastname: Sarsam
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Toulmay
authors.affiliation: Department of Molecular and Cellular Biology, University of California, Davis, Davis, CA 95616.
authors.forename: Justin
authors.initials: J
authors.lastname: Yamada
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.
authors.forename: William A
authors.initials: WA
authors.lastname: Prinz
authors.affiliation: Department of Molecular and Cellular Biology, University of California, Davis, Davis, CA 95616 jmnunnari@ucdavis.edu.
authors.forename: Jodi
authors.initials: J
authors.lastname: Nunnari
mesh_terms: D017920:Antiporters / Q000502:physiology*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D004875:Ergosterol / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000502:physiology*; D015398:Signal Transduction; D051782:Sterol Regulatory Element Binding Protein 2; D013312:Stress, Physiological; D014617:Vacuoles / Q000378:metabolism*
chemical_list: D017920:Antiporters; C000599842:LTC1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D051782:Sterol Regulatory Element Binding Protein 2; D004875:Ergosterol