1
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Proline metabolism regulates replicative lifespan in the yeast Saccharomyces cerevisiae

      brief-report

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          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.

          Related collections

          Most cited references39

          • Record: found
          • Abstract: found
          • Article: not found

          Regulation of yeast replicative life span by TOR and Sch9 in response to nutrients.

          Calorie restriction increases life span in many organisms, including the budding yeast Saccharomyces cerevisiae. From a large-scale analysis of 564 single-gene-deletion strains of yeast, we identified 10 gene deletions that increase replicative life span. Six of these correspond to genes encoding components of the nutrient-responsive TOR and Sch9 pathways. Calorie restriction of tor1D or sch9D cells failed to further increase life span and, like calorie restriction, deletion of either SCH9 or TOR1 increased life span independent of the Sir2 histone deacetylase. We propose that the TOR and Sch9 kinases define a primary conduit through which excess nutrient intake limits longevity in yeast.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae.

            Calorie restriction extends life-span in a wide variety of organisms. Although it has been suggested that calorie restriction may work by reducing the levels of reactive oxygen species produced during respiration, the mechanism by which this regimen slows aging is uncertain. Here, we mimicked calorie restriction in yeast by physiological or genetic means and showed a substantial extension in life-span. This extension was not observed in strains mutant for SIR2 (which encodes the silencing protein Sir2p) or NPT1 (a gene in a pathway in the synthesis of NAD, the oxidized form of nicotinamide adenine dinucleotide). These findings suggest that the increased longevity induced by calorie restriction requires the activation of Sir2p by NAD.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              The Saccharomyces cerevisiae zinc finger proteins Msn2p and Msn4p are required for transcriptional induction through the stress response element (STRE).

              The MSN2 and MSN4 genes encode homologous and functionally redundant Cys2His2 zinc finger proteins. A disruption of both MSN2 and MSN4 genes results in a higher sensitivity to different stresses, including carbon source starvation, heat shock and severe osmotic and oxidative stresses. We show that MSN2 and MSN4 are required for activation of several yeast genes such as CTT1, DDR2 and HSP12, whose induction is mediated through stress-response elements (STREs). Msn2p and Msn4p are important factors for the stress-induced activation of STRE dependent promoters and bind specifically to STRE-containing oligonucleotides. Our results suggest that MSN2 and MSN4 encode a DNA-binding component of the stress responsive system and it is likely that they act as positive transcription factors.
                Bookmark

                Author and article information

                Journal
                Microb Cell
                Microb Cell
                Microb Cell
                Microb Cell
                Microbial Cell
                Shared Science Publishers OG
                2311-2638
                24 September 2019
                07 October 2019
                : 6
                : 10
                : 482-490
                Affiliations
                [1 ]Department of Frontier Bioscience, Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, 1266 Tamura, Nagahama, Shiga 526-0829, Japan.
                [2 ]Division of Biological Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara 630-0192, Japan.
                Author notes
                * Corresponding Author: Yukio Mukai, Department of Frontier Bioscience, Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, 1266 Tamura, Nagahama, Shiga 526-0829, Japan; Tel.: +81-749-64-8163; Fax: +81-749-64-8140; E-mail: y_mukai@ 123456nagahama-i-bio.ac.jp ;
                # Corresponding Author: Hiroshi Takagi, Division of Biological Science, Graduate School of Science and Technology, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara 630-0192, Japan; Tel.: +81-743-72-5420; Fax: +81-743-72-5429; E-mail: hiro@ 123456bs.naist.jp

                Conflict of interest: The authors declare no conflict of interest.

                Please cite this article as: Yukio Mukai, Yuka Kamei, Xu Liu, Shan Jiang, Yukiko Sugimoto, Noreen Suliani binti Mat Nanyan, Daisuke Watanabe and Hiroshi Takagi ( 2019). Proline metabolism regulates replicative lifespan in the yeast Saccharomyces cerevisiae. Microbial Cell 6(10): 482-490. doi: 10.15698/mic2019.10.694

                Article
                MIC0179E118
                10.15698/mic2019.10.694
                6780008
                fcb961e7-3220-41c1-ae0f-e3a81874d999
                Copyright @ 2019

                This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.

                History
                : 29 April 2019
                : 19 August 2019
                : 16 September 2019
                Funding
                We are grateful to P. O. Ljungdahl (Stockholm University) for the generous gift of yeast strains. This work was supported by a Grant-in-Aid for Challenging Exploratory Research (19K22282) from Japan Society for the Promotion of Science (JSPS) to HT and a grant from the Project of the NARO Bio-oriented Technology Research Advancement Institution (Research program on development of innovative technology) (30017B) to HT.
                Categories
                Research Report
                Proline
                Replicative Lifespan
                Stress Response
                Amino Acid Metabolism
                Yeast

                proline,replicative lifespan,stress response,amino acid metabolism,yeast

                Comments

                Comment on this article