Department of Pathology and Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, California 94143, USA.
J Cell Sci. 2021 Jun 1;134(11). doi: 10.1242/jcs.253781. Epub 2021 Jun 7.
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 in 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. 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.
在酿酒酵母中，线粒体的选择性自噬降解，称为线粒体自噬，受到衔接蛋白 Atg32 的严格调控。尽管我们了解了 Atg32 控制线粒体自噬的分子机制，但它在酵母生存和适应能力方面的生理作用仍不明确。在这里，我们证明了 Atg32 在促进呼吸生长期间精胺产生和热诱导的线粒体应激中的作用。在呼吸生长期间，由于精胺及其生物合成前体 S-腺苷甲硫氨酸的生物合成受损，线粒体自噬缺陷的酵母在热应激诱导的生长和生存能力方面表现出严重缺陷。此外，精胺的产生对于热应激期间诱导细胞保护性一氧化氮（NO）至关重要。因此，向 Atg32 突变酵母中添加精胺足以增强 NO 的产生，并在热应激期间恢复呼吸生长。我们的发现揭示了酵母线粒体自噬在精胺代谢中的先前未被认识的生理作用，并阐明了线粒体自噬、多胺生物合成和 NO 信号之间的新联系。
