Extension of yeast chronological lifespan by methylamine.

Extension of yeast chronological lifespan by methylamine.
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DOI:
10.1371/journal.pone.0048982
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
van der Klei IJ
van der Klei IJ
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Kumar S;Lefevre SD;Veenhuis M;van der Klei IJ

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酵母细胞的时间衰老通常被用作人类有丝分裂后细胞衰老的模型。在硫酸铵存在下,在葡萄糖上生长的酿酒酵母主要用于酵母老化研究。我们分析了在需要初级过氧化物酶体代谢的条件下生长的酵母菌的时间老化。相对于不需要过氧化物酶体的葡萄糖,在甲醇或乙醇上生长的细胞,在过氧化物酶体酶的代谢下生长的多形镰刀菌的按时间顺序的寿命大大延长。H. polymorpha对葡萄糖的寿命较短主要是由于培养基酸化,而ROS很可能不起重要作用。细胞在甲醇/甲胺上生长,而不是在甲醇/硫酸铵上生长,进一步延长了细胞的寿命。这与介质酸化无关。我们表明,在碳饥饿条件下,过氧化物酶胺氧化酶氧化甲胺是延长寿命的原因。甲胺氧化产物甲醛被进一步氧化,导致NADH的生成,这有助于增加ATP的生成和减少固定阶段的ROS水平。我们的结论是,初级过氧化物酶体代谢提高了多形血鼠的按时间顺序的寿命。此外,通过有机氮源在碳饥饿条件下产生NADH的可能性支持进一步延长细胞寿命。因此,酵母CLS分析的解释应该包括对细胞能量状态的可能影响。
Chronological aging of yeast cells is commonly used as a model for aging of human post-mitotic cells. The yeast Saccharomyces cerevisiae grown on glucose in the presence of ammonium sulphate is mainly used in yeast aging research. We have analyzed chronological aging of the yeast Hansenula polymorpha grown at conditions that require primary peroxisome metabolism for growth. The chronological lifespan of H. polymorpha is strongly enhanced when cells are grown on methanol or ethanol, metabolized by peroxisome enzymes, relative to growth on glucose that does not require peroxisomes. The short lifespan of H. polymorpha on glucose is mainly due to medium acidification, whereas most likely ROS do not play an important role. Growth of cells on methanol/methylamine instead of methanol/ammonium sulphate resulted in further lifespan enhancement. This was unrelated to medium acidification. We show that oxidation of methylamine by peroxisomal amine oxidase at carbon starvation conditions is responsible for lifespan extension. The methylamine oxidation product formaldehyde is further oxidized resulting in NADH generation, which contributes to increased ATP generation and reduction of ROS levels in the stationary phase. We conclude that primary peroxisome metabolism enhanced chronological lifespan of H. polymorpha. Moreover, the possibility to generate NADH at carbon starvation conditions by an organic nitrogen source supports further extension of the lifespan of the cell. Consequently, the interpretation of CLS analyses in yeast should include possible effects on the energy status of the cell.
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