AUTHOR=Kim Yeong Hyeock , Ryu Ji-In , Devare Mayur Nimbadas , Jung Juhye , Kim Jeong-Yoon 

TITLE=The intricate role of Sir2 in oxidative stress response during the post-diauxic phase in Saccharomyces cerevisiae

JOURNAL=Frontiers in Microbiology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2023.1285559

DOI=10.3389/fmicb.2023.1285559

ISSN=1664-302X

ABSTRACT=<p>Silent information regulator 2 (Sir2) is a conserved NAD<sup>+</sup>-dependent histone deacetylase crucial for regulating cellular stress response and the aging process in <italic>Saccharomyces cerevisiae</italic>. In this study, we investigated the molecular mechanism underlying how the absence of Sir2 can lead to altered stress susceptibilities in <italic>S. cerevisiae</italic> under different environmental and physiological conditions. In a glucose-complex medium, the <italic>sir2</italic>Δ strain showed increased sensitivity to H<sub>2</sub>O<sub>2</sub> compared to the wild-type strain during the post-diauxic phase. In contrast, it displayed increased resistance during the exponential growth phase. Transcriptome analysis of yeast cells in the post-diauxic phase indicated that the <italic>sir2</italic>Δ mutant expressed several oxidative defense genes at lower levels than the wild-type, potentially accounting for its increased susceptibility to H<sub>2</sub>O<sub>2</sub>. Interestingly, however, the <italic>sir2</italic>Δ<italic>ras2</italic>Δ double mutant exhibited greater resistance to H<sub>2</sub>O<sub>2</sub> than the <italic>ras2</italic>Δ single mutant counterpart. We found that the expression regulation of the cytoplasmic catalase encoded by <italic>CTT1</italic> was critical for the increased resistance to H<sub>2</sub>O<sub>2</sub> in the <italic>sir2</italic>Δ<italic>ras2</italic>Δ strain. The expression of the <italic>CTT1</italic> gene was influenced by the combined effect of <italic>RAS2</italic> deletion and the transcription factor Azf1, whose level was modulated by Sir2. These findings provide insights into the importance of understanding the intricate interactions among various factors contributing to cellular stress response.</p>