Proline metabolism regulates replicative lifespan in the yeast Saccharomyces cerevisiae
In many plants and microorganisms, intracellular proline has a protective role against various stresses, including heat-shock, oxidation and osmolarity. Environmental stresses induce cellular senescence in a variety of eukaryotes. Here we showed that intracellular proline regulates the replicative l...
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Shared Science Publishers OG
2019-09-01
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| Series: | Microbial Cell |
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| Online Access: | http://microbialcell.com/researcharticles/2019a-mukai-microbial-cell/ |
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| author | Yukio Mukai Yuka Kamei Xu Liu Shan Jiang Yukiko Sugimoto Noreen Suliani binti Mat Nanyan Daisuke Watanabe Hiroshi Takagi |
| author_facet | Yukio Mukai Yuka Kamei Xu Liu Shan Jiang Yukiko Sugimoto Noreen Suliani binti Mat Nanyan Daisuke Watanabe Hiroshi Takagi |
| author_sort | Yukio Mukai |
| collection | DOAJ |
| description | In many plants and microorganisms, intracellular proline has a protective role against various stresses, including heat-shock, oxidation and osmolarity. Environmental stresses induce cellular senescence in a variety of eukaryotes. Here we showed that intracellular proline regulates the replicative lifespan in the budding yeast Saccharomyces cerevisiae. Deletion of the proline oxidase gene PUT1 and expression of the γ-glutamate kinase mutant gene PRO1-I150T that is less sensitive to feedback inhibition accumulated proline and extended the replicative lifespan of yeast cells. Inversely, disruption of the proline biosynthetic genes PRO1, PRO2, and CAR2 decreased stationary proline level and shortened the lifespan of yeast cells. Quadruple disruption of the proline transporter genes unexpectedly did not change intracellular proline levels and replicative lifespan. Overexpression of the stress-responsive transcription activator gene MSN2 reduced intracellular proline levels by inducing the expression of PUT1, resulting in a short lifespan. Thus, the intracellular proline levels at stationary phase was positively correlated with the replicative lifespan. Furthermore, multivariate analysis of amino acids in yeast mutants deficient in proline metabolism showed characteristic metabolic profiles coincident with longevity: acidic and basic amino acids and branched-chain amino acids positively contributed to the replicative lifespan. These results allude to proline metabolism having a physiological role in maintaining the lifespan of yeast cells. |
| format | Article |
| id | doaj-art-2905fe837e3f489da4ab33e9082035bb |
| institution | OA Journals |
| issn | 2311-2638 |
| language | English |
| publishDate | 2019-09-01 |
| publisher | Shared Science Publishers OG |
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| series | Microbial Cell |
| spelling | doaj-art-2905fe837e3f489da4ab33e9082035bb2025-08-20T02:05:20ZengShared Science Publishers OGMicrobial Cell2311-26382019-09-0161048249010.15698/mic2019.10.694Proline metabolism regulates replicative lifespan in the yeast Saccharomyces cerevisiaeYukio Mukai0Yuka Kamei1Xu Liu2Shan Jiang3Yukiko Sugimoto4Noreen Suliani binti Mat Nanyan5Daisuke Watanabe6Hiroshi Takagi7Department of Frontier Bioscience, Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, 1266 Tamura, Nagahama, Shiga 526-0829, Japan.Department of Frontier Bioscience, Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, 1266 Tamura, Nagahama, Shiga 526-0829, Japan.Department of Frontier Bioscience, Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, 1266 Tamura, Nagahama, Shiga 526-0829, Japan.Department of Frontier Bioscience, Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, 1266 Tamura, Nagahama, Shiga 526-0829, Japan.Division of Biological Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara 630-0192, Japan.Division of Biological Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara 630-0192, Japan.Division of Biological Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara 630-0192, Japan.Division of Biological Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara 630-0192, Japan.In many plants and microorganisms, intracellular proline has a protective role against various stresses, including heat-shock, oxidation and osmolarity. Environmental stresses induce cellular senescence in a variety of eukaryotes. Here we showed that intracellular proline regulates the replicative lifespan in the budding yeast Saccharomyces cerevisiae. Deletion of the proline oxidase gene PUT1 and expression of the γ-glutamate kinase mutant gene PRO1-I150T that is less sensitive to feedback inhibition accumulated proline and extended the replicative lifespan of yeast cells. Inversely, disruption of the proline biosynthetic genes PRO1, PRO2, and CAR2 decreased stationary proline level and shortened the lifespan of yeast cells. Quadruple disruption of the proline transporter genes unexpectedly did not change intracellular proline levels and replicative lifespan. Overexpression of the stress-responsive transcription activator gene MSN2 reduced intracellular proline levels by inducing the expression of PUT1, resulting in a short lifespan. Thus, the intracellular proline levels at stationary phase was positively correlated with the replicative lifespan. Furthermore, multivariate analysis of amino acids in yeast mutants deficient in proline metabolism showed characteristic metabolic profiles coincident with longevity: acidic and basic amino acids and branched-chain amino acids positively contributed to the replicative lifespan. These results allude to proline metabolism having a physiological role in maintaining the lifespan of yeast cells.http://microbialcell.com/researcharticles/2019a-mukai-microbial-cell/prolinereplicative lifespanstress responseamino acid metabolismyeast |
| spellingShingle | Yukio Mukai Yuka Kamei Xu Liu Shan Jiang Yukiko Sugimoto Noreen Suliani binti Mat Nanyan Daisuke Watanabe Hiroshi Takagi Proline metabolism regulates replicative lifespan in the yeast Saccharomyces cerevisiae Microbial Cell proline replicative lifespan stress response amino acid metabolism yeast |
| title | Proline metabolism regulates replicative lifespan in the yeast Saccharomyces cerevisiae |
| title_full | Proline metabolism regulates replicative lifespan in the yeast Saccharomyces cerevisiae |
| title_fullStr | Proline metabolism regulates replicative lifespan in the yeast Saccharomyces cerevisiae |
| title_full_unstemmed | Proline metabolism regulates replicative lifespan in the yeast Saccharomyces cerevisiae |
| title_short | Proline metabolism regulates replicative lifespan in the yeast Saccharomyces cerevisiae |
| title_sort | proline metabolism regulates replicative lifespan in the yeast saccharomyces cerevisiae |
| topic | proline replicative lifespan stress response amino acid metabolism yeast |
| url | http://microbialcell.com/researcharticles/2019a-mukai-microbial-cell/ |
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