Dysregulation of very-long-chain fatty acid metabolism causes membrane saturation and induction of the unfolded protein response
| Autor: | Jeffrey N. Agar, Walid M. Abdelmoula, Sankha S. Basu, Nathalie Y. R. Agar, Begoña Gimenez-Cassina Lopez, Yagmur Micoogullari, Nina Weisshaar, John Hanna, Jessie Ang, Nicholas D. Schmitt |
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| Rok vydání: | 2019 |
| Předmět: |
endocrine system
Saccharomyces cerevisiae Proteins endocrine system diseases Very long chain fatty acid Biosynthesis and Biodegradation Saccharomyces cerevisiae Biology Endoplasmic Reticulum 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Coenzyme A Ligases Homeostasis Molecular Biology Cholesterol homeostasis 030304 developmental biology 0303 health sciences Membranes Fatty Acids Cell Biology Metabolism Articles Endoplasmic Reticulum Stress Fatty Acid Transport Proteins Lipid Metabolism Lipids Membrane chemistry Biochemistry Unfolded protein response Unfolded Protein Response Saturation (chemistry) Protein quality 030217 neurology & neurosurgery |
| Zdroj: | Molecular Biology of the Cell |
| ISSN: | 1939-4586 |
| Popis: | The unfolded protein response (UPR) senses defects in the endoplasmic reticulum (ER) and orchestrates a complex program of adaptive cellular remodeling. Increasing evidence suggests an important relationship between lipid homeostasis and the UPR. Defects in the ER membrane induce the UPR, and the UPR in turn controls the expression of some lipid metabolic genes. Among lipid species, the very-long-chain fatty acids (VLCFAs) are relatively rare and poorly understood. Here, we show that loss of the VLCFA-coenzyme A synthetase Fat1, which is essential for VLCFA utilization, results in ER stress with compensatory UPR induction. Comprehensive lipidomic analyses revealed a dramatic increase in membrane saturation in the fat1Δ mutant, likely accounting for UPR induction. In principle, this increased membrane saturation could reflect adaptive membrane remodeling or an adverse effect of VLCFA dysfunction. We provide evidence supporting the latter, as the fat1Δ mutant showed defects in the function of Ole1, the sole fatty acyl desaturase in yeast. These results indicate that VLCFAs play essential roles in protein quality control and membrane homeostasis and suggest an unexpected requirement for VLCFAs in Ole1 function. |
| Databáze: | OpenAIRE |
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