Glutathione peroxidase 4 (Gpx4) counteracts mitochondrial lipid peroxidation in mammals. In yeast, Gpx2 is orthologous of Gpx4, is localized in mitochondria, and reduces both inorganic and organic peroxides. However, a phenotype of oxidative stress hypersensitivity has not been observed with gpx2 deletion. We hypothesized that the absence of polyunsaturated fatty acids (PUFA) in yeast membranes may mask an antioxidant role of Gpx2 in mitochondria. Thus, we tested the effects of PUFA on cell viability, mitochondrial function, ROS production, and mitochondrial fatty acid composition of a gpx2Δ mutant subjected to chronological aging. As expected, gpx2Δ mutation did not alter these parameters with respect to wild-type (WT) cells after 30 h growth, even in the presence of linolenic acid (C18:3), except for some activities of the electron transport chain (ETC) complexes. Conversely, aged gpx2Δ cells exhibited lower viability, impaired respiration, decreased ETC activities, and increased ROS generation in comparison to aged WT cells. These effects were exacerbated by C18:3, as gpx2Δ cells displayed residual respiration, full inhibition of ETC complexes, and a burst in ROS production on day 15 that decreased on day 30, although ROS remained several-fold higher than in WT cells. gpx2 was not involved in the preservation of PUFA levels, as no differences in mitochondrial C18:3 content were observed between WT and gpx2Δ cells. These results indicate that gpx2 is a late - acting antioxidant system that decreases mitochondrial ROS production and preserves ETC function, without being involved in the preservation of PUFA levels in mitochondria.
Keywords: Yeast; aging; electron transport chain; glutathione peroxidase; polyunsaturated fatty acids.