Leucine depletion extends the lifespans of leucine-auxotrophic fission yeast by inducing Ecl1 family genes via the transcription factor Fil1
Leucine depletion extends the lifespans of leucine-auxotrophic fission yeast by inducing Ecl1 family genes via the transcription factor Fil1
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DOI：
10.1007/s00438-019-01592-6
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发表时间：
2019-08
影响因子：
3.1
通讯作者：
Hokuto Ohtsuka;Takanori Kato;Teppei Sato;Takafumi Shimasaki;Takaaki Kojima;H. Aiba
中科院分区：
文献类型：
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作者：
Hokuto Ohtsuka;Takanori Kato;Teppei Sato;Takafumi Shimasaki;Takaaki Kojima;H. Aiba
许多研究表明，各种模式生物的寿命可以通过限制增殖所必需的营养物质的数量来延长。在schizosaccharomyces pombe中，Ecl1家族基因与寿命控制有关，并且是细胞对营养耗竭的反应所必需的，但其功能和作用机制尚不清楚。在这里，我们表明亮氨酸的消耗延长了亮氨酸营养不良细胞的时间寿命（CLS）。此外，亮氨酸的消耗延长了CLS，导致细胞小型化和细胞周期阻滞在G1期，所有这些过程都依赖于Ecl1家族基因。尽管亮氨酸的缺失使亮氨酸-营养不良细胞中ecl1+的表达提高了约100倍，但这些条件并不影响亮氨酸-营养不良fil1突变体中tecl1+的表达，这些突变体是在使用79个破坏转录因子的突变体的删除集筛选中分离出来的。Fil1是一种gata型锌指转录因子，据报道直接结合到ecl1+和ecl2+的上游区域。因此，我们认为Ecl1家族基因是在对环境胁迫（如氧化应激和热应激）或氮、硫源或氨基酸亮氨酸的营养枯竭的响应中诱导的。我们还提出，这些基因在维持细胞存活中发挥重要作用，直到有利于增殖的条件恢复。
Many studies show that lifespans of various model organisms can be extended by limiting the quantities of nutrients that are necessary for proliferation. InSchizosaccharomyces 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 ofecl1+by about 100-fold in leucine-auxotrophic cells, these conditions did not affectecl1+expression in leucine-auxotrophicfil1mutants 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 ofecl1+andecl2+. 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.