MET18 Deficiency Increases the Sensitivity of Yeast to Oxidative Stress and Shortens Replicative Lifespan by Inhibiting Catalase Activity.

Ya-Qin Chen,Jie Ruan,Wei Zhao,Xin-Guang Liu,Zhiguang Tu,Hongjing Cui,Yuan Yuan

doi:10.1155/2017/7587395

Ya-Qin Chen, Jie Ruan + Show 5 more

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https://doi.org/10.1155/2017/7587395

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Abstract

Yeast MET18, a subunit of the cytosolic iron-sulfur (Fe/S) protein assembly (CIA) machinery which is responsible for the maturation of Fe/S proteins, has been reported to participate in the oxidative stress response. However, the underlying molecular mechanisms remain unclear. In this study, we constructed a MET18/met18Δ heterozygous mutant yeast strain and found that MET18 deficiency in yeast cells impaired oxidative stress resistance as evidenced by increased sensitivity to hydrogen peroxide (H2O2) and cumene hydroperoxide (CHP). Mechanistically, the mRNA levels of catalase A (CTA1) and catalase T (CTT1) as well as the total catalase activity were significantly reduced in MET18-deficient cells. In contrast, overexpression of CTT1 or CTA1 in MET18-deficient cells significantly increased the intracellular catalase activity and enhanced the resistance ability against H2O2 and CHP. In addition, MET18 deficiency diminished the replicative capacity of yeast cells as evidenced by the shortened replicative lifespan, which can be restored by CTT1 overexpression, but not by CTA1, in the MET18-deficient cells. These results suggest that MET18, in a catalase-dependent manner, plays an essential role in enhancing the resistance of yeast cells to oxidative stress and increasing the replicative capacity of yeast cells.

Highlights

Oxygen (O2) is crucial for the livelihood of organisms grown aerobically
To investigate the role of MET18 in yeast response to oxidative stress, we constructed a MET18/met18Δ mutant strain which was confirmed by a real-time polymerase chain reaction (PCR) detection of MET18- and URA3-specific PCR products
Our results suggest that MET18 deficiency increases the cellular response of yeast to H2O2 and cumene hydroperoxide (CHP) and shortens replicative lifespan (RLS) through downregulation of catalases CTT1 and CTA1

Summary

Introduction

Exposure to higher O2 concentration can increase the production of reactive oxygen species (ROS), including hydroxyl radical (OH−), hydrogen peroxide (H2O2), and superoxide anions (O2−), which may exert detrimental effects on cell growth. The effects of environmental oxygen concentrations on the intracellular ROS production are highly dependent upon the culture medium, the cells themselves, the metabolic state of the cells, and the presence of any antioxidative compound or enzyme and other known and unknown factors [1,2,3]. It has been shown that culturing cells in air (21% O2) exposes the cells to much higher levels of oxygen than what they are usually submitted to under physiological conditions (2∼5% O2) [2]. The underlying mechanisms remain largely unknown [3, 4]

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