Cellular homoeostatic pathways such as macroautophagy (hereinafter autophagy) are regulated by basic mechanisms that are conserved throughout the eukaryotic kingdom. However, it remains poorly understood how these mechanisms further evolved in higher organisms. Here we describe a modification in the autophagy pathway in vertebrates, which promotes its activity in response to oxidative stress. We have identified two oxidation-sensitive cysteine residues in a prototypic autophagy receptor SQSTM1/p62, which allow activation of pro-survival autophagy in stress conditions. The Drosophila p62 homologue, Ref(2)P, lacks these oxidation-sensitive cysteine residues and their introduction into the protein increases protein turnover and stress resistance of flies, whereas perturbation of p62 oxidation in humans may result in age-related pathology. We propose that the redox-sensitivity of p62 may have evolved in vertebrates as a mechanism that allows activation of autophagy in response to oxidative stress to maintain cellular homoeostasis and increase cell survival.

中文翻译：

---

SQSTM1/p62 的氧化介导氧化还原状态和蛋白质稳态之间的联系。

细胞稳态途径如巨自噬（以下称自噬）受整个真核生物界保守的基本机制调节。然而，这些机制如何在高等生物中进一步进化仍然知之甚少。在这里，我们描述了脊椎动物自噬途径的一种修饰，它促进了其响应氧化应激的活性。我们已经确定了原型自噬受体 SQSTM1/p62 中的两个氧化敏感半胱氨酸残基，它们允许在应激条件下激活促生存自噬。果蝇 p62 同源物 Ref(2)P 缺乏这些对氧化敏感的半胱氨酸残基，它们引入蛋白质会增加蛋白质周转和果蝇的抗逆性，而人类 p62 氧化的扰动可能会导致与年龄相关的病理。