PUFA-induced cell death is mediated by Yca1p-dependent and -independent pathways, and is reduced by vitamin C in yeast

FEMS Yeast Research
Magnus JohanssonDina Petranovic

Abstract

Polyunsaturated fatty acids (PUFA) such as linoleic acid (LA, n-6, C18:2) and γ-linolenic acid (GLA, n-6, C18:3) are essential and must be obtained from the diet. There has been a growing interest in establishing a bio-sustainable production of PUFA in several microorganisms, e.g. in yeast Saccharomyces cerevisiae. However, PUFAs can also be toxic to cells because of their susceptibility to peroxidation. Here we investigated the negative effects of LA and GLA production on S. cerevisiae by characterizing a strain expressing active Δ6 and Δ12 desaturases from the fungus Mucor rouxii. Previously, we showed that the PUFA-producing strain has low viability, down-regulated genes for oxidative stress response, and decreased proteasome activity. Here we show that the PUFA strain accumulates high levels of reactive oxygen species (ROS) and lipid peroxides, and accumulates damaged proteins. The PUFA strain also showed great increase in metacaspase Yca1p activity, suggesting cells could die by caspase-mediated cell death. When treated with antioxidant vitamin C, ROS, lipid peroxidation and protein carbonylation were greatly reduced, and the activity of the metacaspase was significantly decreased too, ultimately doubling the lifespan of t...Continue Reading

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Citations

Oct 6, 2020·Oxidative Medicine and Cellular Longevity·Chainika KhatanaAdesh K Saini
Jan 5, 2021·Annals of Geriatric Medicine and Research·Gulperi Yalcin, Cheol-Koo Lee
Nov 28, 2017·Bioresource Technology·Xiao-Man SunHe Huang
May 14, 2021·Metabolic Engineering·Olena P IshchukDina Petranovic
Nov 16, 2021·Critical Reviews in Biotechnology·Yu-Lei JiaQi Li

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