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Study on the Response of Fatty Acid Elongase Defects to Lipid Metabolism and Oleic Acid Stress in Saccharomyces cerevisiae
Cheng Xun1, Du Xiuxiu1, Wang Handong2, Huang Zhiwei1*, Deng Yunxia1, Shen Yuhu2,3*
1Key Lab of Science & Technology of Eco-textile (Ministry of Education), College of Chemistry & Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, China; 2Key Laboratory of Crop Molecular Breeding of Qinghai Province, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining 810008, China; 3Key Laboratory of Adaptation and Evolution of Plateau Biota, Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining 810008, China
Abstract: Biomedical evidence shows that excessive fat， especially fatty acids (FA) accumulation in non-adipose tissues can cause lipid metabolism disorder， leading to cellular dysfunction or necrosis. The fatty acid elongase family participates in fatty acid metabolism， which is highly conserved in eukaryotes in fatty acid metabolism and is closely related to the metabolism of membrane lipids. However， the relationship between fatty acid elongases and cellular lipotoxic effect is unclear. In this study， Saccharomyces cerevisiae was used as our cellular model due to the advantages of easy characterization and convenient genetic manipulation in lipid metabolism. By comparing the response of fatty acid elongase-deficient elo1Δ， elo2Δ and elo3Δ with that of wild-type yeast to different fatty acids， we found that long-chain fatty acid elongases ELO2 and ELO3 defects were highly sensitive to oleic acid. Cell lipid droplets and neutral lipid metabolism played a key role in maintaining cellular lipid homeostasis. Our results showed that the synthesis defects of long chain fatty acids or oleic acid could promote formation of cell lipid droplets， and significantly enhanced the synthesis of the cellular neutral lipids (TAG) and cholesterol ester (SE). The fatty acid composition were analyzed by gas chromatography-mass spectrometry (GC-MS). C26 fatty acids were barely detected， while C20 and C22 fatty acids accumulated in elo3Δ strain. The content of C26 fatty acid was also decreased significantly in elo2Δ strain. However， the treatment of oleic acid increased the proportion of the total very long-chain fatty acid in the BY4741 cells， and the ratios of unsaturated fatty acids to saturated fatty acids were increased in elo2Δ and elo3Δ strains. On the contrary， the overexpression of long-chain fatty acid elongase genes could significantly reduce the content of oleic acid compared to the wild-type strain. Based on the study of the responses of fatty acid elongase defects to lipid metabolism and oleic acid stress in the model cells of Saccharomyces cerevisiae， it provides basic data for the investigation of lipid metabolism disorder and lipotoxicity effect in medicine.
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