Sulfur sequestration promotes multicellularity during nutrient limitation.

Sulfur sequestration promotes multicellularity during nutrient limitation.
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硫螯合促进多细胞在营养限制。

DOI:
10.1038/s41586-021-03270-3
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发表时间:
2021-03
期刊:
影响因子:
64.8
通讯作者:
Pearce EL
Pearce EL
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Kelly B;Carrizo GE;Edwards-Hicks J;Sanin DE;Stanczak MA;Priesnitz C;Flachsmann LJ;Curtis JD;Mittler G;Musa Y;Becker T;Buescher JM;Pearce EL

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盘基网柄藻的行为依赖于营养物质。当有足够的食物时,这些变形虫以单细胞状态存在,但当饥饿时,它们聚集成多细胞生物体。这种生物学特性使盘状杜父菌成为研究基本代谢如何控制细胞分化和功能的理想模型。在这里,我们表明,活性氧物种产生的营养限制的结果,导致半胱氨酸的螯合在抗氧化剂谷胱甘肽。这种螯合限制了半胱氨酸的硫原子在有助于线粒体代谢和细胞增殖的过程中的使用,例如蛋白质翻译和含有铁-硫簇的酶的活性。受调节的硫螯合使盘状杜父菌保持在非增殖状态,为多细胞发育铺平了道路。这种通过活性氧的信号传导机制突出了氧和硫作为决定早期真核生物细胞命运的简单信号传导分子,并影响了多细胞真核生物对营养波动的反应。剥夺单细胞盘基网柄藻的营养物质产生活性氧,其在谷胱甘肽内螯合半胱氨酸,这使这种阿米巴维持在非增殖状态,促进聚集成多细胞生物体。
The behaviour of Dictyostelium discoideum depends on nutrients. When sufficient food is present these amoebae exist in a unicellular state, but upon starvation they aggregate into a multicellular organism. This biology makes D. discoideum an ideal model for investigating how fundamental metabolism commands cell differentiation and function. Here we show that reactive oxygen species—generated as a consequence of nutrient limitation—lead to the sequestration of cysteine in the antioxidant glutathione. This sequestration limits the use of the sulfur atom of cysteine in processes that contribute to mitochondrial metabolism and cellular proliferation, such as protein translation and the activity of enzymes that contain an iron–sulfur cluster. The regulated sequestration of sulfur maintains D. discoideum in a nonproliferating state that paves the way for multicellular development. This mechanism of signalling through reactive oxygen species highlights oxygen and sulfur as simple signalling molecules that dictate cell fate in an early eukaryote, with implications for responses to nutrient fluctuations in multicellular eukaryotes. Depriving unicellular Dictyostelium discoideum of nutrients generates reactive oxygen species that sequester cysteine within glutathione, which maintains this amoeba in a nonproliferating state that promotes aggregation into a multicellular organism.
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