PUFA-induced cell death is mediated by Yca1p-dependent and -independent pathways, and is reduced by vitamin C in yeast
Journal article, 2016

Polyunsaturated fatty acids (PUFA) such as linoleic acid (LA, n-6, C18:2) and gamma-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 Delta 6 and Delta 12 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 the PUFA strain. When deleting YCA1, the caspase-like activity and the oxidative stress decreased and although the lifespan was slightly prolonged, the phenotype could not be fully reversed, pointing that Yca1p was not the main executor of cell death.

saccharomyces-cerevisiae

polyunsaturated fatty-acids

caspase

polyunsaturated fatty acids

oxidative stress

protein carbonylation

lipid peroxidation

Author

Magnus Johansson

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Xin Chen

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Stefina Milanova

Chalmers, Biology and Biological Engineering

Cristiano Santos

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Dina Petranovic Nielsen

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

FEMS Yeast Research

1567-1356 (ISSN) 1567-1364 (eISSN)

Vol. 16 2 fow007

Subject Categories

Microbiology

DOI

10.1093/femsyr/fow007

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4/5/2022 6