QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 18, Issue 4, 1359-1365, April 2007

This Article Full Text Full Text (PDF) All Versions of this Article: E06-08-0718v1 E06-08-0718v2 18/4/1359    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Farah, M. E. Articles by Amberg, D. C. Search for Related Content PubMed PubMed Citation Articles by Farah, M. E. Articles by Amberg, D. C.

Conserved Actin Cysteine Residues Are Oxidative Stress Sensors That Can Regulate Cell Death in Yeast

Department of Biochemistry and Molecular Biology, State University of New York Upstate Medical University, Syracuse, NY 13210

Submitted August 16, 2006; Revised January 8, 2007; Accepted January 31, 2007
Monitoring Editor: Charles Boone

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 oye2 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.

Address correspondence to: David Charles Amberg (ambergd{at}upstate.edu)

Abbreviations used: NAC, N-acetyl-L-cysteine; OYE, old yellow enzyme; ROS, reactive oxygen species.