Pyruvate kinase variant of fission yeast tunes carbon metabolism, cell regulation, growth and stress resistance
Pyruvate kinase variant of fission yeast tunes carbon metabolism, cell regulation, growth and stress resistance
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DOI：
10.15252/msb.20199270
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发表时间：
2020-04-01
影响因子：
9.9
通讯作者：
Bahler, Jurg
中科院分区：
文献类型：
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作者：
Kamrad, Stephan;Grossbach, Jan;Bahler, Jurg
细胞平衡糖酵解与呼吸，以支持其在不同环境或生理背景下的代谢需求。由于葡萄糖丰富，许多细胞更喜欢通过有氧糖酵解或发酵生长。利用161个自然分离的裂殖酵母，我们调查了发酵-呼吸平衡的遗传基础和表型效应。实验室和其他一些菌株更多地依赖于呼吸。这种特性与Pyk1保守区域的单核苷酸多态性有关，Pyk1是裂殖酵母中唯一的丙酮酸激酶。该变体降低Pyk1活性和糖酵解通量。用"高活性"等位基因替换实验室菌株中的"低活性" pyk1等位基因足以增加发酵和降低呼吸。这种代谢再平衡引发了转录组和蛋白质组以及细胞特征的系统水平调整，包括增加生长和时间寿命，但降低了对氧化应激的抵抗力。因此，低Pyk1活性不会导致生长优势，但胁迫耐受性。糖酵解通量的遗传调节可能反映了缺乏丙酮酸激酶亚型的物种的适应性权衡。
Cells balance glycolysis with respiration to support their metabolic needs in different environmental or physiological contexts. With abundant glucose, many cells prefer to grow by aerobic glycolysis or fermentation. Using 161 natural isolates of fission yeast, we investigated the genetic basis and phenotypic effects of the fermentation-respiration balance. The laboratory and a few other strains depended more on respiration. This trait was associated with a single nucleotide polymorphism in a conserved region of Pyk1, the sole pyruvate kinase in fission yeast. This variant reduced Pyk1 activity and glycolytic flux. Replacing the "low-activity" pyk1 allele in the laboratory strain with the "high-activity" allele was sufficient to increase fermentation and decrease respiration. This metabolic rebalancing triggered systems-level adjustments in the transcriptome and proteome and in cellular traits, including increased growth and chronological lifespan but decreased resistance to oxidative stress. Thus, low Pyk1 activity does not lead to a growth advantage but to stress tolerance. The genetic tuning of glycolytic flux may reflect an adaptive trade-off in a species lacking pyruvate kinase isoforms.