Conserved actin cysteine residues are oxidative stress sensors that can regulate cell death in yeast.
Actin's functional complexity makes it a likely target of oxidative stress but also places it in a prime position to coordinate the response to oxidative stress. We have previously shown that the NADPH oxidoreductase Oye2p protects the actin cytoskeleton from oxidative stress. Here we demonstrate that the physiological consequence of actin oxidation is to accelerate cell death in yeast. Loss of Oye2p leads to reactive oxygen species accumulation, activation of the oxidative stress response, nuclear fragmentation and DNA degradation, and premature chronological aging of yeast cells. The oye2Delta phenotype can be completely suppressed by removing the potential for formation of the actin C285-C374 disulfide bond, the likely substrate of the Oye2p enzyme or by treating the cells with the clinically important reductant N-acetylcysteine. Because these two cysteines are coconserved in all actin isoforms, we theorize that we have uncovered a universal mechanism whereby actin helps to coordinate the cellular response to oxidative stress by both sensing and responding to oxidative load.
Farah
Michelle E
ME
Department of Biochemistry and Molecular Biology, State University of New York Upstate Medical University, Syracuse, NY 13210, USA.
Amberg
David C
DC
D000111:Acetylcysteine / Q000494:pharmacology; D000199:Actins / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000975:Antioxidants / Q000494:pharmacology; D017124:Conserved Sequence; D003545:Cysteine; D003599:Cytoskeleton / Q000378:metabolism; D004220:Disulfides; D009154:Mutation; D009252:NADPH Dehydrogenase / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
D000199:Actins; D000975:Antioxidants; D004220:Disulfides; D017382:Reactive Oxygen Species; D029701:Saccharomyces cerevisiae Proteins; D009252:NADPH Dehydrogenase; D003545:Cysteine; D000111:Acetylcysteine