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Genome-Wide Fitness and Expression Profiling Implicate Mga2 in Adaptation to Hydrogen Peroxide

Creator:

PLoS Genetics

Type: Report
Region: Republic of Ireland
Northern Ireland
Description:

Program in Bioinformatics, University of California San Diego, La Jolla, California, United States of America, 2 Department of Bioengineering, University of California San Diego, La Jolla, California, United States of AmericaAbstract Caloric restriction extends lifespan, an effect once thought to involve attenuation of reactive oxygen species (ROS) generated by aerobic metabolism. However, recent evidence suggests that caloric restriction may in fact raise ROS levels, which in turn provides protection from acute doses of oxidant through a process called adaptation. To shed light on the molecular mechanisms of adaptation, we designed a series of genome-wide deletion fitness and mRNA expression screens to identify genes involved in adaptation to hydrogen peroxide. Combined with known transcriptional interactions, the integrated data implicate Yap1 and Skn7 as central transcription factors of both the adaptive and acute oxidative responses. They also identify the transcription factors Mga2 and Rox1 as active exclusively in the adaptive response and show that Mga2 is essential for adaptation. These findings are striking because Mga2 and Rox1 have been thought to control the response to hypoxic, not oxidative, conditions. Expression profiling of mga2Δ and rox1Δ knockouts shows that these factors most strongly regulate targets in ergosterol, fatty-acid, and zinc metabolic pathways. Direct quantitation of ergosterol reveals that its basal concentration indeed depends on Mga2, but that Mga2 is not required for the decrease in ergosterol observed during adaptation.Author Summary Reactive oxygen species (ROS) damage a variety of structures within the cell, resulting in disease and aging. In a seemingly paradoxical effect termed adaptation, it is possible to prevent damage caused by ROS by pre-treating the cell with a small amount of oxidant. We studied this process in order to identify the mechanisms that provide this protection. Our study identified a number of genes and processes with previously unappreciated roles in adaptation. The mechanisms we identified are remarkable because they are distinct from those previously known to protect the cell from ROS. Although this study is conducted in yeast, the wide conservation of adaptation among many organisms suggests that the results from this study may be widely applicable.Citation: Kelley R, Ideker T (2009) Genome-Wide Fitness and Expression Profiling Implicate Mga2 in Adaptation to Hydrogen Peroxide. PLoS Genet 5(5): e1000488. doi:10.1371/journal.pgen.1000488Editor: Greg Gibson, The University of Queensland, Australia Received: August 27, 2008; Accepted: April 21, 2009; Published: May 29, 2009Copyright: © 2009 Kelley, Ideker. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Funding: This work was generously supported by grant ES014811 from the National Institute of Environmental Health Sciences (NIEHS). TI is a David and Lucille Packard Fellow. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Competing interests: The authors have declared that no competing interests exist.* E-mail: trey@bioeng.ucsd.edu 

Date:

01/06/2009

Rights: Public
Suggested citation:

PLoS Genetics. (2009) Genome-Wide Fitness and Expression Profiling Implicate Mga2 in Adaptation to Hydrogen Peroxide [Online]. Available from: http://publichealthwell.ie/node/9268 [Accessed: 20th November 2019].

  

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