TY - JOUR
T1 - Ltc1 is an ER-localized sterol transporter and a component of ER-mitochondria and ER-vacuole contacts
AU - Murley, Andrew
AU - Sarsam, Reta D.
AU - Toulmay, Alexandre
AU - Yamada, Justin
AU - Prinz, William A.
AU - Nunnari, Jodi
N1 - Funding Information:
We thank Dr. Michael Paddy in the University of California, Davis (UC Davis) MCB-CBS Imaging Facility for advice with fluorescence microscopy. We also thank Dr. Brett Finney and Mr. Darren Weber from the UC Davis Proteomics Core Facility for mass spectrometric analysis of protein samples. Finally, we thank members of the Nunnari, Prinz, and Powers laboratories for stimulating discussion. A. Murley was supported by National Institutes of Health (NIH) training grant 5T32GM007377-34; J. Nunnari is supported by NIH grants R01GM062942, R01GM097432, and R01GM106019. J. Nunnari is on the Scientific Advisory Board of Mitobridge, Inc. The authors declare no other competing financial interests.
Publisher Copyright:
© 2015 Murley et al.
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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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U2 - 10.1083/jcb.201502033
DO - 10.1083/jcb.201502033
M3 - Article
C2 - 25987606
AN - SCOPUS:84951019875
SN - 0021-9525
VL - 209
SP - 539
EP - 548
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 4
ER -