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- The NADP+-dependent glutamate dehydrogenase Gdh1 is subjected to glucose starvation-induced reversible aggregation that affects stress resistance in yeast
- Woo Hyun Lee , Ju Yeong Oh , Pil Jae Maeng
- J. Microbiol. 2019;57(10):884-892. Published online August 3, 2019
- DOI: https://doi.org/10.1007/s12275-019-9065-z
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- 3 Citations
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Abstract
- The yeast Saccharomyces cerevisiae has two isoforms of NADP+-dependent glutamate dehydrogenase (Gdh1 and Gdh3) that catalyze the synthesis of glutamate from α-ketoglutarate and NH4 +. In the present study, we confirmed that Gdh3, but not Gdh1, mainly contributes to the oxidative stress resistance of stationary-phase cells and found evidence suggesting that the insignificance of Gdh1 to stress resistance is possibly resulted from conditional and reversible aggregation of Gdh1 into punctuate foci initiated in parallel with postdiauxic growth. Altered localization to the mitochondria or peroxisomes prevented Gdh1, which was originally localized in the cytoplasm, from stationary phase-specific aggregation, suggesting that some cytosolic factors are involved in the process of Gdh1 aggregation. Glucose starvation triggered the transition of the soluble form of Gdh1 into the insoluble aggregate form, which could be redissolved by replenishing glucose, without any requirement for protein synthesis. Mutational analysis showed that the N-terminal proximal region of Gdh1 (NTP1, aa 21-26, TLFEQH) is essential for glucose starvation-induced aggregation. We also found that the substitution of NTP1 with the corresponding region of Gdh3 (NTP3) significantly increased the contribution of the mutant Gdh1 to the stress resistance of stationary-phase cells. Thus, this suggests that NTP1 is responsible for the negligible role of Gdh1 in maintaining the oxidative stress resistance of stationary- phase cells and the stationary phase-specific stresssensitive phenotype of the mutants lacking Gdh3.
Research Support, Non-U.S. Gov't
- Growth Phase-dependent Roles of Sir2 in Oxidative Stress Resistance and Chronological Lifespan in Yeast
- Woo Kyu Kang , Yeong Hyeock Kim , Byoung-Soo Kim , Jeong-Yoon Kim
- J. Microbiol. 2014;52(8):652-658. Published online July 5, 2014
- DOI: https://doi.org/10.1007/s12275-014-4173-2
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- 9 Citations
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Abstract
- Silent Information Regulator 2 (Sir2), a conserved NAD+- dependent histone deacetylase, has been implicated as one of the key factors in regulating stress response and longevity. Here, we report that the role of Sir2 in oxidative stress resistance and chronological lifespan is dependent on growth phase in yeast. In exponential phase, sir2Δ cells were more resistant to H2O2 stress and had a longer chronological lifespan than wild type. By contrast, in post-diauxic phase, sir2Δ cells were less resistant to H2O2 stress and had a shorter chronological lifespan than wild type cells. Similarly, the expression of antioxidant genes, which are essential to cope with oxidative stress, was regulated by Sir2 in a growth phasedependent manner. Collectively, our findings highlight the importance of the metabolic state of the cell in determining whether Sir2 can protect against or accelerate cellular aging of yeast.
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