Center for Experimental Medicine, the First Affiliated Hospital, Nanchang University, Nanchang, China; Department of General Medicine, the First Affiliated Hospital, Nanchang University, Nanchang, China.
Department of Molecular Medicine, the University of Texas Health, San Antonio, TX, 78229, USA.
Biochem Biophys Res Commun. 2020 Jan 29;522(1):254-258. doi: 10.1016/j.bbrc.2019.11.089. Epub 2019 Nov 21.
Autophagy is a highly conserved biological process essential to protein, cellular and organismal homeostasis. As autophagy plays a critical role in cellular responses to various external and internal stimuli, it is important to understand the mechanism underlying autophagy regulation. Here, we monitor the stability of 17 key autophagy factors in the yeast S. cerevisiae and show that Atg9 and Atg14 are degraded under normal growth conditions. Whereas Atg14 is regulated by both the proteasome and autophagy, Atg9 turnover is normally mediated by the proteasome but impeded upon starvation or rapamycin treatment. Interestingly, distinct segments of Atg9 confer instability, suggesting that multiple pathways are involved in Atg9 degradation. Our results provide the foundation to further elucidate the physiological significance of Atg9 turnover and also the interplay between two major proteolytic systems (i.e., autophagy and the proteasome).
自噬是一种高度保守的生物学过程，对蛋白质、细胞和机体的动态平衡至关重要。由于自噬在细胞对各种外部和内部刺激的反应中起着关键作用，因此了解自噬调节的机制非常重要。在这里，我们监测了酵母 S. cerevisiae 中 17 种关键自噬因子的稳定性，并表明 Atg9 和 Atg14 在正常生长条件下会降解。虽然 Atg14 受到蛋白酶体和自噬的双重调节，但在饥饿或雷帕霉素处理时，Atg9 的周转通常由蛋白酶体介导，但受到阻碍。有趣的是，Atg9 的不同片段赋予其不稳定性，表明有多种途径参与了 Atg9 的降解。我们的研究结果为进一步阐明 Atg9 周转的生理意义以及两种主要的蛋白水解系统（即自噬和蛋白酶体）之间的相互作用提供了基础。
