Heat stress induced nitric oxide (DAF-FM-DA) response in respiratory growing Wild-type, atg32∆ and spe1∆ mutant yeast with and without spermidine addition

In Saccharomyces cerevisiae, the selective autophagic degradation of mitochondria, termed mitophagy, is critically regulated by the adapter protein, Atg32. Despite our knowledge about the molecular mechanisms by which Atg32 controls mitophagy, its physiological roles on yeast survival and fitness remains less clear. Here, we demonstrate a requirement for Atg32 in promoting spermidine production during respiratory growth and heat-induced mitochondrial stress. During respiratory growth, mitophagy-deficient yeast exhibit profound heat-stress induced defects in growth and viability due to impaired biosynthesis of spermidine and its biosynthetic precursor S-Adenosyl-Methionine (SAM). Moreover, spermidine production is crucial for the induction of cytoprotective nitric oxide (NO) during heat stress. Hence, the re-addition of spermidine to Atg32 mutant yeast is sufficient to both enhance NO production and restore respiratory growth during heat stress. Our findings uncover a previously unrecognized physiological role for yeast mitophagy in spermidine metabolism and illuminate new interconnections between mitophagy, polyamine biosynthesis and NO signaling.

在酿酒酵母（Saccharomyces cerevisiae）中，线粒体选择性自噬（mitophagy）的关键调控过程由衔接蛋白Atg32介导。尽管我们已阐明Atg32调控线粒体自噬的分子机制，但其对酵母存活与适应度的生理功能仍尚不明确。本研究证实，在呼吸生长与热诱导线粒体应激过程中，Atg32是促进亚精胺（spermidine）合成所必需的。在呼吸生长阶段，线粒体自噬缺陷型酵母因亚精胺及其生物合成前体S-腺苷甲硫氨酸（S-Adenosyl-Methionine, SAM）的合成受阻，会出现严重的热应激诱导性生长与存活缺陷。此外，热应激期间亚精胺的生成对于细胞保护性一氧化氮（nitric oxide, NO）的诱导具有关键作用。因此，向Atg32突变酵母重新添加亚精胺，即可同时促进NO生成并恢复热应激条件下的呼吸生长能力。本研究揭示了酵母线粒体自噬在亚精胺代谢中此前未被认知的生理功能，并阐明了线粒体自噬、多胺生物合成与NO信号通路之间全新的交互关联。

搜集汇总

背景与挑战

背景概述

该数据集包含热应激诱导的一氧化氮（通过DAF-FM-DA检测）响应实验数据，涉及呼吸生长的野生型、atg32∆和spe1∆突变酵母，并添加或不添加亚精胺处理。数据集旨在研究酵母线粒体自噬（mitophagy）在亚精胺代谢和一氧化氮信号传导中的作用，揭示了Atg32蛋白对热应激耐受性的关键影响。数据包括荧光显微镜成像的量化结果，支持了线粒体自噬与多胺生物合成之间的新联系。