Orm1 and Orm2 are conserved endoplasmic reticulum membrane proteins regulating lipid homeostasis and protein quality control
- Han, Sumin Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, USA
- Lone, Museer A. Department of Medicine, Division of Biochemistry, University of Fribourg, Switzerland
- Schneiter, Roger Department of Medicine, Division of Biochemistry, University of Fribourg, Switzerland
- Chang, Amy Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, USA
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2010
Published in:
- Proceedings of the National Academy of Sciences. - 2010, vol. 107, no. 13, p. 5851-5856
English
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.
- Faculty
- Faculté des sciences et de médecine
- Department
- Département de Biologie
- Language
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- English
- Classification
- Biological sciences
- License
- License undefined
- Identifiers
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- RERO DOC 17629
- DOI 10.1073/pnas.0911617107
- Persistent URL
- https://folia.unifr.ch/unifr/documents/301433
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