Han, Sumin Lone, Museer A. Schneiter, Roger Chang, Amy 2010 Yeast members of the ORMDL family of endoplasmic reticulum (ER) membrane proteins play a central role in lipid homeostasis and protein quality control. In the absence of yeast Orm1 and Orm2, accumulation of long chain base, a sphingolipid precursor, suggests dysregulation of sphingolipid synthesis. Physical interaction between Orm1 and Orm2 and serine palmitoyltransferase, responsible for the first committed step in sphingolipid synthesis, further supports a role for the Orm proteins in regulating sphingolipid synthesis. Phospholipid homeostasis is also affected in orm1∆ orm2∆ cells: the cells are inositol auxotrophs with impaired transcriptional regulation of genes encoding phospholipid biosynthesis enzymes. Strikingly, impaired growth of orm1∆ orm2∆ cells is associated with constitutive unfolded protein response, sensitivity to stress, and slow ER-to-Golgi transport. Inhibition of sphingolipid synthesis suppresses orm1∆ orm2∆ phenotypes, including ER stress, suggesting that disrupted sphingolipid homeostasis accounts for pleiotropic phenotypes. Thus, the yeast Orm proteins control membrane biogenesis by coordinating lipid homeostasis with protein quality control. application/pdf https://folia.unifr.ch/global/documents/301433 https://folia.unifr.ch/documents/301433/files/sch_ooc.pdf https://folia.unifr.ch/documents/301433/files/sch_ooc_sm.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.0911617107 info:eu-repo/semantics/openAccess License undefined Proceedings of the National Academy of Sciences. - 2010, vol. 107, no. 13, p. 5851-5856 membrane biogenesis sphingolipid synthesis unfolded protein response info:eu-repo/classification/udc/57 Orm1 and Orm2 are conserved endoplasmic reticulum membrane proteins regulating lipid homeostasis and protein quality control http://purl.org/coar/resource_type/c_6501