@article{3e67453a2a684dae96935ddf55c6723b,
title = "A lipid E-MAP identifies Ubx2 as a critical regulator of lipid saturation and lipid bilayer stress",
abstract = "Biological membranes are complex, and the mechanisms underlying their homeostasis are incompletely understood. Here, we present a quantitative genetic interaction map (E-MAP) focused on various aspects of lipid biology, including lipid metabolism, sorting, and trafficking. This E-MAP contains \textasciitilde{}250,000 negative and positive genetic interaction scores and identifies a molecular crosstalk of protein quality control pathways with lipid bilayer homeostasis. Ubx2p, a component of the endoplasmic-reticulum-associated degradation pathway, surfaces as a key upstream regulator of the essential fatty acid (FA) desaturase Ole1p. Loss of Ubx2p affects the transcriptional control of OLE1, resulting in impaired FA desaturation and a severe shift toward more saturated membrane lipids. Both the induction of the unfolded protein response and aberrant nuclear membrane morphologies observed in cells lacking UBX2 are suppressed by the supplementation of unsaturated FAs. Our results point toward the existence of dedicated bilayer stress responses for membrane homeostasis.",
author = "Surma, \{Michal A.\} and Christian Klose and Debby Peng and Michael Shales and Caroline Mrejen and Adam Stefanko and Hannes Braberg and Gordon, \{David E.\} and Daniela Vorkel and Ejsing, \{Christer S.\} and Robert Farese and Kai Simons and Krogan, \{Nevan J.\} and Robert Ernst",
note = "Funding Information: The authors acknowledge Pablo Aguilar, Erin Currie, Mark Hochstrasser, Robin W. Klemm, Stefan Jentsch, Thomas Sommer, Maya Schuldiner, Andrej Shevchenko, Dieter Wolf, Peter Walter, Tobias Walther, and Jonathan Weissman for help and/or reagents and James Saenz and Daniel Lingwood for critically reading the manuscript. R.E. acknowledges Jin Ye, Ray Deshaies, and Pedro Carvalho for sharing unpublished data. This work was supported by the German Research Foundation (ER608/2-1 and SFB807 Transport and Communication across Biological Membranes to R.E.), the National Institutes of Health (GM084448, GM084279, GM081879, and GM098101 to N.J.K. and GM099844 to R.F.), the European Molecular Biology Organization (ALTF 379-2008 to R.E. and ASTF 219-2009 to M.A.S.), the European Science Foundation LIPIDPROD program (SI459/3-1 to K.S.), Lundbeckfonden (95-310-13591 to C.S.E.), the Danish Council for Independent Research (09-72484 to C.S.E.), and the Klaus Tschira Foundation (to K.S.). N.J.K. is a Searle scholar and Keck young investigator. ",
year = "2013",
month = aug,
day = "22",
doi = "10.1016/j.molcel.2013.06.014",
language = "English",
volume = "51",
pages = "519--530",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "4",
}