Accumulation of long-chain bases in yeast promotes their conversion to a long-chain base vinyl ether
- Martínez-Montañés, Fernando Department of Biology,* University of Fribourg, Switzerland
- Lone, Museer A. Department of Biology,* University of Fribourg, Switzerland
- Hsu, Fong-Fu Department of Internal Medicine, Washington University School of Medicine, St. Louis, USA
- Schneiter, Roger Department of Biology,* University of Fribourg, Switzerland
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11.01.2016
Published in:
- Journal of Lipid Research. - 2016, vol. 57, no. 11, p. 2040–2050
English
Long-chain bases (LCBs) are the precursors to ceramide and sphingolipids in eukaryotic cells. They are formed by the action of serine palmitoyl-CoA transferase (SPT), a complex of integral membrane proteins located in the endoplasmic reticulum. SPT activity is negatively regulated by Orm proteins to prevent the toxic overaccumulation of LCBs. Here we show that overaccumulation of LCBs in yeast results in their conversion to a hitherto undescribed LCB derivative, an LCB vinyl ether. The LCB vinyl ether is predominantly formed from phytosphingosine (PHS) as revealed by conversion of odd chain length tracers C17-dihydrosphingosine and C17- PHS into the corresponding LCB vinyl ether derivative. PHS vinyl ether formation depends on ongoing acetyl-CoA synthesis, and its levels are elevated when the LCB degradative pathway is blocked by deletion of the major LCB kinase, LCB4, or the LCB phosphate lyase, DPL1. PHS vinyl ether formation thus appears to constitute a shunt for the LCB phosphate- and lyase-dependent degradation of LCBs. Consistent with a role of PHS vinyl ether formation in LCB detoxification, the lipid is efficiently exported from the cells.
- 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 278434
- DOI 10.1194/jlr.M070748
- Persistent URL
- https://folia.unifr.ch/unifr/documents/305193
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