Cells have distinct mechanisms to maintain protection against different reactive oxygen species: Oxidative-stress-response genes

Abstract

The complete set of viable deletion strains in Saccharomyces cerevisiae was screened for sensitivity of mutants to five oxidants to identify cell functions involved in resistance to oxidative stress. This screen identified a unique set of mainly constitutive functions providing the first line of defense against a particular oxidant; these functions are very dependent on the nature of the oxidant. Most of these functions are distinct from those involved in repair and recovery from damage, which are generally induced in response to stress, because there was little correlation between mutant sensitivity and the reported transcriptional response to oxidants of the relevant gene. The screen identified 456 mutants sensitive to at least one of five different types of oxidant, and these were ranked in order of sensitivity. Many genes identified were not previously known to have a role in resistance to reactive oxygen species. These encode functions including protein sorting, ergosterol metabolism, autophagy, and vacuolar acidification. Only two mutants were sensitive to all oxidants examined, only 12 were sensitive to at least four, and different oxidants had very different spectra of deletants that were sensitive. These findings highlight the specificity of cellular responses to different oxidants: No single oxidant is representative of general oxidative stress. Mitochondrial respiratory functions were overrepresented in mutants sensitive to H2O2, and vacuolar protein-sorting mutants were enriched in mutants sensitive to diamide. Core functions required for a broad range of oxidative-stress resistance include transcription, protein trafficking, and vacuolar function.

Transmembrane protein 85 from both human (TMEM85) and yeast (YGL231c) inhibit hydrogen peroxide mediated cell death in yeast

“…1B-D). These results are consistent with the notion that different genes are required to protect cells against different stresses [21].…”

“…3B). The analysis of the complete set of viable gene deletion strains from yeast has lead to the identification of several hundred genes that are re- quired for complete resistance to oxidative stresses including H 2 O 2 [21]. Our results are consistent with this study since YGL231c was not identified in the screen.…”

Assessment of chronological lifespan dependent molecular damages in yeast lacking mitochondrial antioxidant genes

“…Among these genes, deletion of CCS1 showed the highest sensitivity to both diamide and menadione. This is inline with a previous study which also showed that sod1D cells were sensitive to both menadione and diamide [22]. …”

Characterization of a CuZn superoxide dismutase gene in the arbuscular mycorrhizal fungus Glomus intraradices

“…It has been demonstrated that the deletion of single genes in the ergosterol synthesis pathway rendered yeast cells more susceptible to oxidative stress (Branco et al 2004; Thorpe et al 2004). In addition, H2O2 was found to repress the ergosterol biosynthesis pathway through Pof14, a new member of the Fbox protein family, which binds and decreases the activity of the squalene synthase ERG9, a key enzyme in ergosterol metabolism, leading to a decrease of the total cellular ergosterol levels in Schizosaccharomyces pombe (Tafforeau et al 2006).…”