Ice2 promotes ER membrane biogenesis in yeast by inhibiting the conserved lipin phosphatase complex

EMBO J. 2021 Nov 15;40(22):e107958. doi: 10.15252/embj.2021107958. Epub 2021 Oct 6.

Abstract

Cells dynamically adapt organelle size to current physiological demand. Organelle growth requires membrane biogenesis and therefore needs to be coordinated with lipid metabolism. The endoplasmic reticulum (ER) can undergo massive expansion, but the underlying regulatory mechanisms are largely unclear. Here, we describe a genetic screen for factors involved in ER membrane expansion in budding yeast and identify the ER transmembrane protein Ice2 as a strong hit. We show that Ice2 promotes ER membrane biogenesis by opposing the phosphatidic acid phosphatase Pah1, called lipin in metazoa. Specifically, Ice2 inhibits the conserved Nem1-Spo7 complex and thus suppresses the dephosphorylation and activation of Pah1. Furthermore, Ice2 cooperates with the transcriptional regulation of lipid synthesis genes and helps to maintain cell homeostasis during ER stress. These findings establish the control of the lipin phosphatase complex as an important mechanism for regulating ER membrane biogenesis.

Keywords: Opi1; endoplasmic reticulum; lipid droplets; lipin; organelle biogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Endoplasmic Reticulum / genetics
  • Endoplasmic Reticulum / metabolism*
  • Endoplasmic Reticulum Stress
  • Gene Expression Regulation, Fungal
  • Intracellular Membranes / metabolism*
  • Lipid Metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Multiprotein Complexes / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Organic Chemicals / metabolism
  • Phosphatidate Phosphatase / genetics
  • Phosphatidate Phosphatase / metabolism*
  • Phosphorylation
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Unfolded Protein Response

Substances

  • Ice2 protein, S cerevisiae
  • Membrane Proteins
  • Multiprotein Complexes
  • Nem1 protein, S cerevisiae
  • Nuclear Proteins
  • OPI1 protein, S cerevisiae
  • Organic Chemicals
  • Repressor Proteins
  • SPO7 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • lipine
  • PAH1 protein, S cerevisiae
  • Phosphatidate Phosphatase