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Leucine depletion extends the lifespans of leucine-auxotrophic fission yeast by inducing Ecl1 family genes via the transcription factor Fil1.
Mol Genet Genomics. 2019 Dec; 294(6):1499-1509.MG

Abstract

Many studies show that lifespans of various model organisms can be extended by limiting the quantities of nutrients that are necessary for proliferation. In Schizosaccharomyces pombe, the Ecl1 family genes have been associated with lifespan control and are necessary for cell responses to nutrient depletion, but their functions and mechanisms of action remain uncharacterized. Herein, we show that leucine depletion extends the chronological lifespan (CLS) of leucine-auxotrophic cells. Furthermore, depletion of leucine extended CLS and caused cell miniaturization and cell cycle arrest at the G1 phase, and all of these processes depended on Ecl1 family genes. Although depletion of leucine raises the expression of ecl1+ by about 100-fold in leucine-auxotrophic cells, these conditions did not affect ecl1+ expression in leucine-auxotrophic fil1 mutants that were isolated in deletion set screens using 79 mutants disrupting a transcription factor. Fil1 is a GATA-type zinc finger transcription factor that reportedly binds directly to the upstream regions of ecl1+ and ecl2+. Accordingly, we suggest that Ecl1 family genes are induced in response to environmental stresses, such as oxidative stress and heat stress, or by nutritional depletion of nitrogen or sulfur sources or the amino acid leucine. We also propose that these genes play important roles in the maintenance of cell survival until conditions that favor proliferation are restored.

Authors+Show Affiliations

Laboratory of Molecular Microbiology, Graduate School of Pharmaceutical Sciences, Nagoya University, Chikusa-ku, Nagoya, 464-8601, Japan.Laboratory of Molecular Microbiology, Graduate School of Pharmaceutical Sciences, Nagoya University, Chikusa-ku, Nagoya, 464-8601, Japan.Laboratory of Molecular Microbiology, Graduate School of Pharmaceutical Sciences, Nagoya University, Chikusa-ku, Nagoya, 464-8601, Japan.Laboratory of Molecular Microbiology, Graduate School of Pharmaceutical Sciences, Nagoya University, Chikusa-ku, Nagoya, 464-8601, Japan.Laboratory of Molecular Biotechnology, Graduate School of Bioagricultural Sciences, Nagoya University, Chikusa-ku, Nagoya, 464-8601, Japan.Laboratory of Molecular Microbiology, Graduate School of Pharmaceutical Sciences, Nagoya University, Chikusa-ku, Nagoya, 464-8601, Japan. aiba@ps.nagoya-u.ac.jp.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31456006

Citation

Ohtsuka, Hokuto, et al. "Leucine Depletion Extends the Lifespans of Leucine-auxotrophic Fission Yeast By Inducing Ecl1 Family Genes Via the Transcription Factor Fil1." Molecular Genetics and Genomics : MGG, vol. 294, no. 6, 2019, pp. 1499-1509.
Ohtsuka H, Kato T, Sato T, et al. Leucine depletion extends the lifespans of leucine-auxotrophic fission yeast by inducing Ecl1 family genes via the transcription factor Fil1. Mol Genet Genomics. 2019;294(6):1499-1509.
Ohtsuka, H., Kato, T., Sato, T., Shimasaki, T., Kojima, T., & Aiba, H. (2019). Leucine depletion extends the lifespans of leucine-auxotrophic fission yeast by inducing Ecl1 family genes via the transcription factor Fil1. Molecular Genetics and Genomics : MGG, 294(6), 1499-1509. https://doi.org/10.1007/s00438-019-01592-6
Ohtsuka H, et al. Leucine Depletion Extends the Lifespans of Leucine-auxotrophic Fission Yeast By Inducing Ecl1 Family Genes Via the Transcription Factor Fil1. Mol Genet Genomics. 2019;294(6):1499-1509. PubMed PMID: 31456006.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Leucine depletion extends the lifespans of leucine-auxotrophic fission yeast by inducing Ecl1 family genes via the transcription factor Fil1. AU - Ohtsuka,Hokuto, AU - Kato,Takanori, AU - Sato,Teppei, AU - Shimasaki,Takafumi, AU - Kojima,Takaaki, AU - Aiba,Hirofumi, Y1 - 2019/08/27/ PY - 2019/03/17/received PY - 2019/06/28/accepted PY - 2019/8/29/pubmed PY - 2019/11/12/medline PY - 2019/8/29/entrez KW - Chronological lifespan KW - Ecl1 family gene KW - Fission yeast KW - Leucine KW - ecl1 + KW - fil1 + SP - 1499 EP - 1509 JF - Molecular genetics and genomics : MGG JO - Mol Genet Genomics VL - 294 IS - 6 N2 - Many studies show that lifespans of various model organisms can be extended by limiting the quantities of nutrients that are necessary for proliferation. In Schizosaccharomyces pombe, the Ecl1 family genes have been associated with lifespan control and are necessary for cell responses to nutrient depletion, but their functions and mechanisms of action remain uncharacterized. Herein, we show that leucine depletion extends the chronological lifespan (CLS) of leucine-auxotrophic cells. Furthermore, depletion of leucine extended CLS and caused cell miniaturization and cell cycle arrest at the G1 phase, and all of these processes depended on Ecl1 family genes. Although depletion of leucine raises the expression of ecl1+ by about 100-fold in leucine-auxotrophic cells, these conditions did not affect ecl1+ expression in leucine-auxotrophic fil1 mutants that were isolated in deletion set screens using 79 mutants disrupting a transcription factor. Fil1 is a GATA-type zinc finger transcription factor that reportedly binds directly to the upstream regions of ecl1+ and ecl2+. Accordingly, we suggest that Ecl1 family genes are induced in response to environmental stresses, such as oxidative stress and heat stress, or by nutritional depletion of nitrogen or sulfur sources or the amino acid leucine. We also propose that these genes play important roles in the maintenance of cell survival until conditions that favor proliferation are restored. SN - 1617-4623 UR - https://www.unboundmedicine.com/medline/citation/31456006/Leucine_depletion_extends_the_lifespans_of_leucine_auxotrophic_fission_yeast_by_inducing_Ecl1_family_genes_via_the_transcription_factor_Fil1_ L2 - https://doi.org/10.1007/s00438-019-01592-6 DB - PRIME DP - Unbound Medicine ER -