TOR and MAP kinase pathways synergistically regulate autophagy in response to nutrient depletion in fission yeast

TOR and MAP kinase pathways synergistically regulate autophagy in response to nutrient depletion in fission yeast
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DOI:
10.1080/15548627.2021.1935522
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发表时间:
2021-06-24
期刊:
影响因子:
13.3
通讯作者:
Hidalgo, Elena
Hidalgo, Elena
中科院分区:
生物学1区
文献类型:
--
作者:
Corral-Ramos, Cristina;Barrios, Ruben;Hidalgo, Elena

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一般自噬是真核生物中进化上保守的过程,通过该过程,细胞内物质被运输到溶酶体或空泡内并在溶酶体或空泡内降解,其主要目标是在饥饿期间回收这些物质。自噬的分子基础在酿酒酵母中已被广泛描述,并且Atg蛋白在该过程中的特定作用首次在该模型系统中被表征。在粟酒裂殖酵母中已经做出了重要贡献,突出了自噬中Atg组分的进化相似性和多样性。然而,关于这种遥远的酵母中自噬的信号,途径和作用知之甚少。在这里,我们采取了一种全球性的方法来研究自噬激活的信号,途径和后果。我们证明,不仅氮,但几种营养缺乏,包括缺乏碳,硫,磷或亮氨酸来源,触发自噬,和TORC 1,TORC 2和MAP激酶Sty1通路控制自噬的发生。此外,我们确定了一个意想不到的表型的自噬缺陷的突变体,即他们无法生存在没有亮氨酸时,这种氨基酸的生物合成受损。
General autophagy is an evolutionarily conserved process in eukaryotes, by which intracellular materials are transported into and degraded inside lysosomes or vacuoles, with the main goal of recycling those materials during periods of starvation. The molecular bases of autophagy have been widely described in Saccharomyces cerevisiae, and the specific roles of Atg proteins in the process were first characterized in this model system. Important contributions have been made in Schizosaccharomyces pombe highlighting the evolutionary similarity and, at the same time, diversity of Atg components in autophagy. However, little is known regarding signals, pathways and role of autophagy in this distant yeast. Here, we undertake a global approach to investigate the signals, the pathways and the consequences of autophagy activation. We demonstrate that not only nitrogen but several nutritional deprivations including lack of carbon, sulfur, phosphorus or leucine sources, trigger autophagy, and that the TORC1, TORC2 and MAP kinase Sty1 pathways control the onset of autophagy. Furthermore, we identify an unexpected phenotype of autophagy-defective mutants, namely their inability to survive in the absence of leucine when biosynthesis of this amino acid is impaired.