Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Cell Biology, endoplasmic reticulum, lipid droplets, lipin, Opi1, organelle biogenesis, ENDOPLASMIC-RETICULUM, SACCHAROMYCES-CEREVISIAE, PHOSPHOLIPID-SYNTHESIS, SECRETORY PATHWAY, CORTICAL ER, PROTEINS, METABOLISM, PHOSPHORYLATION, BIOSYNTHESIS, EXPRESSION, Endoplasmic Reticulum, Endoplasmic Reticulum Stress, Gene Expression Regulation, Fungal, Intracellular Membranes, Lipid Metabolism, Membrane Proteins, Multiprotein Complexes, Nuclear Proteins, Organic Chemicals, Phosphatidate Phosphatase, Phosphorylation, Repressor Proteins, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Unfolded Protein Response, 06 Biological Sciences, 08 Information and Computing Sciences, 11 Medical and Health Sciences, Developmental Biology, 31 Biological sciences, 32 Biomedical and clinical sciences

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.