Background Programmed cell death (PCD) induced by acetic acid, the main by-product released during cellulosic hydrolysis, cast a cloud over lignocellulosic biofuel fermented by Saccharomyces cerevisiae and became a burning problem. Atg22p, an ignored integral membrane protein located in vacuole belongs to autophagy-related genes family; prior study recently reported that it is required for autophagic degradation and efflux of amino acids from vacuole to cytoplasm. It may alleviate the intracellular starvation of nutrition caused by Ac and increase cell tolerance. Therefore, we investigate the role of atg22 in cell death process induced by Ac in which attempt is made to discover new perspectives for better understanding of the mechanisms behind tolerance and more robust industrial strain construction. Results In this study, we compared cell growth, physiological changes in the absence and presence of Atg22p under Ac exposure conditions. It is observed that disruption and overexpression of Atg22p delays and enhances acetic acid-induced PCD, respectively. The deletion of Atg22p in S. cerevisiae maintains cell wall integrity, and protects cytomembrane integrity, fluidity and permeability upon Ac stress by changing cytomembrane phospholipids, sterols and fatty acids. More interestingly, atg22 deletion increases intracellular amino acids to aid yeast cells for tackling amino acid starvation and intracellular acidification. Further, atg22 deletion upregulates series of stress response genes expression such as heat shock protein family, cell wall integrity and autophagy. Conclusions The findings show that Atg22p possessed the new function related to cell resistance to Ac. This may help us have a deeper understanding of PCD induced by Ac and provide a new strategy to improve Ac resistance in designing industrial yeast strains for bioethanol production during lignocellulosic biofuel fermentation.

中文翻译：

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Atg22 基因的缺失有助于减少酿酒酵母中乙酸应激诱导的程序性细胞死亡。

背景 由醋酸（纤维素水解过程中释放的主要副产物）诱导的程序性细胞死亡 (PCD) 给酿酒酵母发酵的木质纤维素生物燃料蒙上了一层阴影，并成为一个亟待解决的问题。Atg22p是一种被忽略的位于液泡中的整合膜蛋白，属于自噬相关基因家族；先前的研究最近报道说，自噬降解和氨基酸从液泡到细胞质的流出是必需的。可缓解Ac引起的细胞内营养缺乏，提高细胞耐受性。因此，我们研究了 atg22 在 Ac 诱导的细胞死亡过程中的作用，试图发现新的视角，以更好地理解耐受性背后的机制和更强大的工业菌株构建。结果 在这项研究中，我们比较了细胞生长，在 Ac 暴露条件下 Atg22p 不存在和存在的生理变化。观察到 Atg22p 的破坏和过表达分别延迟和增强乙酸诱导的 PCD。酿酒酵母中 Atg22p 的缺失可维持细胞壁的完整性，并通过改变细胞膜磷脂、甾醇和脂肪酸来保护细胞膜完整性、流动性和在 Ac 胁迫下的通透性。更有趣的是，atg22 缺失增加了细胞内氨基酸，以帮助酵母细胞解决氨基酸饥饿和细胞内酸化问题。此外，atg22 缺失上调了一系列应激反应基因的表达，如热休克蛋白家族、细胞壁完整性和自噬。结论 研究结果表明Atg22p具有与细胞抗Ac相关的新功能。