A Lipid E-MAP Identifies Ubx2 as a Critical Regulator of Lipid Saturation and Lipid Bilayer Stress

Mol Cell. 2013 Aug 22;51(4):519-30. doi: 10.1016/j.molcel.2013.06.014. Epub 2013 Jul 25.

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 ∼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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Membrane / metabolism*
  • Cells, Cultured
  • Computational Biology
  • Epistasis, Genetic*
  • Fatty Acid Desaturases / genetics
  • Fatty Acid Desaturases / metabolism*
  • Flow Cytometry
  • Homeostasis
  • Immunoprecipitation
  • Lipid Bilayers / metabolism*
  • Lipid Metabolism
  • Membrane Lipids / metabolism*
  • Oligonucleotide Array Sequence Analysis
  • Phosphatidylcholines / metabolism
  • Protein Interaction Mapping
  • Protein Transport
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Stearoyl-CoA Desaturase

Substances

  • Carrier Proteins
  • Lipid Bilayers
  • Membrane Lipids
  • Phosphatidylcholines
  • Saccharomyces cerevisiae Proteins
  • UBX2 protein, S cerevisiae
  • Fatty Acid Desaturases
  • Stearoyl-CoA Desaturase
  • delta-9 fatty acid desaturase