转醛醇酶同工酶 NQM1 与转录因子 VHR1 的杂合增效相互作用影响静止期存活和氧化应激抗性。
A haploproficient interaction of the transaldolase paralogue NQM1 with the transcription factor VHR1 affects stationary phase survival and oxidative stress resistance.
机构信息
Max Planck Institute for Molecular Genetics, Ihnestr 73, Berlin, 14195, Germany.
Department of Biochemistry and Cambridge Systems Biology Center, University of Cambridge, 80, Tennis, Court Road, Cambridge, CB2 1GA, UK.
出版信息
BMC Genet. 2015 Feb 11;16:13. doi: 10.1186/s12863-015-0171-6.
BACKGROUND
Studying the survival of yeast in stationary phase, known as chronological lifespan, led to the identification of molecular ageing factors conserved from yeast to higher organisms. To identify functional interactions among yeast chronological ageing genes, we conducted a haploproficiency screen on the basis of previously identified long-living mutants. For this, we created a library of heterozygous Saccharomyces cerevisiae double deletion strains and aged them in a competitive manner.
RESULTS
Stationary phase survival was prolonged in a double heterozygous mutant of the metabolic enzyme non-quiescent mutant 1 (NQM1), a paralogue to the pentose phosphate pathway enzyme transaldolase (TAL1), and the transcription factor vitamin H response transcription factor 1 (VHR1). We find that cells deleted for the two genes possess increased clonogenicity at late stages of stationary phase survival, but find no indication that the mutations delay initial mortality upon reaching stationary phase, canonically defined as an extension of chronological lifespan. We show that both genes influence the concentration of metabolites of glycolysis and the pentose phosphate pathway, central metabolic players in the ageing process, and affect osmolality of growth media in stationary phase cultures. Moreover, NQM1 is glucose repressed and induced in a VHR1 dependent manner upon caloric restriction, on non-fermentable carbon sources, as well as under osmotic and oxidative stress. Finally, deletion of NQM1 is shown to confer resistance to oxidizing substances.
CONCLUSIONS
The transaldolase paralogue NQM1 and the transcription factor VHR1 interact haploproficiently and affect yeast stationary phase survival. The glucose repressed NQM1 gene is induced under various stress conditions, affects stress resistance and this process is dependent on VHR1. While NQM1 appears not to function in the pentose phosphate pathway, the interplay of NQM1 with VHR1 influences the yeast metabolic homeostasis and stress tolerance during stationary phase, processes associated with yeast ageing.
背景
研究酵母在静止期的存活，即所谓的时序寿命，导致了从酵母到高等生物的保守分子衰老因素的鉴定。为了鉴定酵母时序衰老基因之间的功能相互作用，我们基于先前鉴定的长寿突变体进行了单倍体优势筛选。为此，我们创建了一个异质的酿酒酵母双缺失菌株文库，并以竞争方式对其进行老化。
结果
在代谢酶非静止突变体 1（NQM1）的双杂合突变体中，NQM1 是戊糖磷酸途径酶转醛醇酶（TAL1）的同源物，以及转录因子维生素 H 反应转录因子 1（VHR1）中，静止期存活率延长。我们发现，缺失这两个基因的细胞在静止期存活的晚期具有更高的集落形成能力，但没有迹象表明突变会延迟进入静止期时的初始死亡率，这通常被定义为时序寿命的延长。我们表明，这两个基因都影响糖酵解和戊糖磷酸途径的代谢物浓度，这些都是衰老过程中的核心代谢物，并且影响静止期培养物中生长培养基的渗透压。此外，NQM1 在葡萄糖抑制下，并且在依赖 VHR1 的情况下，在营养限制、非发酵碳源以及在渗透压和氧化应激下被诱导。最后，NQM1 的缺失被证明赋予了对氧化物质的抗性。
结论
转醛醇酶的同源物 NQM1 和转录因子 VHR1 以单倍体优势相互作用，影响酵母静止期的存活。葡萄糖抑制的 NQM1 基因在各种应激条件下被诱导，影响应激抗性，这个过程依赖于 VHR1。虽然 NQM1 似乎不在戊糖磷酸途径中起作用，但 NQM1 与 VHR1 的相互作用影响了酵母静止期代谢平衡和应激耐受，这些过程与酵母衰老有关。
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