A critical role for very long-chain fatty acid elongases in oleic acid-mediated Saccharomyces cerevisiae cytotoxicity
Wang, Qiao1; Du, Xiuxiu1; Ma, Ke2; Shi, Ping3; Liu, Wenbin2; Sun, Jing4; Peng, Min4; Huang, Zhiwei1,4
AbstractElongases FEN1/ELO2 and SUR4/ELO3 are important enzymes involved in the elongation of long-chain fatty acids (LCFAs) to very long-chain fatty acids (VLCFAs) in Saccharomyces cerevisiae. The molecular mechanism of the involvement of these elongases in lipotoxicity is unclear. In the present study, we investigated the role of VLCFA elongases in oleic acid-mediated yeast cytotoxicity. The spot test showed that yeast strains with the deletion of ELO2 or ELO3 were strikingly sensitive to oleic acid, while there was no change on the growth of strain with deleted ELO1 which was involved in the elongation of C-14 fatty acid (FA) to C-16 FA. By using GC-MS, the unsaturation index was increased in elo2(Delta) and elo3(Delta) mutants after treatment with oleic acid (OLA). However, the proportion of VLCFAs was increased in response to OLA in the wild-type strain. The growth inhibition of elo2(Delta) and elo3(Delta) could be partially rescued by two commonly used antioxidant agents N-acetyl cysteine (NAC) and Ascorbic acid (VC). The further study showed that exposure to excess OLA led to an increase in the levels of reactive oxygen species (ROS) and thiobarbituric acid reactive substances (TBARS), and a decline in the quantity of reduced glutathione (GSH) in both the wild type and mutant strains. However, the antioxidant enzyme activities of superoxide dismutase (SOD) and catalase (CAT) were increased in the wild type and elo1(Delta) A strains, while they were significantly decreased in the mutants of elo2(Delta) and elo3(Delta) after treated with excess OLA. Thus, oxidative damage mainly contributed to the cell death induced by OLA in ole2(Delta) and ole3(Delta). Taken together, although disruption of ELO2 or ELO3 did not affect the cellular lipid unsaturation, they altered the distribution and propotion of cellular VLCFAs, leading to the cell membrane impairment, which augmented the ability of OLA to permeabilize the plasma membrane. The data suggest that the very long-chain fatty acids elongases ELO2 and ELO3 play important roles in lipotoxic cell death induced by OLA through maintaining a balanced FA composition in plasma membrane.
KeywordFatty Acids Elongases Very Long-chain Fatty Acids Oleic Acid Lipotoxicity Oxidative Stress Membrane Permeability
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
Indexed BySCI
Funding OrganizationNational Natural Science Foundation of China(31671309) ; Opening Project of Shanghai Key Laboratory of Crime Scene Evidence(2016XCWZK14) ; Development Project of Qinghai Key Laboratory(2017-Z-Y10)
WOS Research AreaMicrobiology
WOS SubjectMicrobiology
WOS IDWOS:000428603200001
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Document Type期刊论文
Affiliation1.Donghua Univ, Coll Chem Chem Engn & Biotechnol, Minist Educ, Key Lab Ecotext, 2999 Renmin Rd, Shanghai 201620, Peoples R China
2.Shanghai Res Inst Criminal Sci & Technol, Shanghai Key Lab Crime Scene Evidence, Zhongshan North 1 Rd, Shanghai 200083, Peoples R China
3.East China Univ Sci & Technol, State Key Lab Bioreactor Engn, 130 Meilong Rd, Shanghai 200237, Peoples R China
4.Chinese Acad Sci, Northwest Inst Plateau Biol, Qinghai Key Lab Qinghai Tibet Plateau Biol Resour, Xiguan Ave 59, Xining 810001 11, Qinghai, Peoples R China
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Wang, Qiao,Du, Xiuxiu,Ma, Ke,et al. A critical role for very long-chain fatty acid elongases in oleic acid-mediated Saccharomyces cerevisiae cytotoxicity[J]. MICROBIOLOGICAL RESEARCH,2018,207:1-7.
APA Wang, Qiao.,Du, Xiuxiu.,Ma, Ke.,Shi, Ping.,Liu, Wenbin.,...&Huang, Zhiwei.(2018).A critical role for very long-chain fatty acid elongases in oleic acid-mediated Saccharomyces cerevisiae cytotoxicity.MICROBIOLOGICAL RESEARCH,207,1-7.
MLA Wang, Qiao,et al."A critical role for very long-chain fatty acid elongases in oleic acid-mediated Saccharomyces cerevisiae cytotoxicity".MICROBIOLOGICAL RESEARCH 207(2018):1-7.
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