Reactive oxygen species are essential for autophagy and specifically regulate the activity of Atg4
Reactive oxygen species are essential for autophagy and specifically regulate the activity of Atg4
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DOI：
10.1038/sj.emboj.7601623
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发表时间：
2007-04-04
期刊：
影响因子：
11.4
通讯作者：
Elazar, Zvulun
中科院分区：
文献类型：
--
作者：
Scherz-Shouval, Ruth;Shvets, Elena;Elazar, Zvulun
自噬是真核细胞降解和循环利用大分子和细胞器的主要分解代谢途径。在环境压力条件下，在发育过程中和各种病理情况下，该途径被激活。在这项研究中，我们描述了活性氧（ROS）作为信号分子在饥饿诱导的自噬中的作用。我们发现饥饿刺激ROS的形成，特别是H2O2。这些氧化条件对于自噬是必不可少的，因为抗氧化剂可以消除自噬体的形成和随后的蛋白质降解。此外，我们确定半胱氨酸蛋白酶HsAtg4是H2O2氧化的直接靶标，并指定位于HsAtg4催化位点附近的半胱氨酸残基是这一调控的关键。该调控突变体的表达阻止了细胞中自噬体的形成，从而为自噬过程的氧化还原调控提供了一种分子机制。
Autophagy is a major catabolic pathway by which eukaryotic cells degrade and recycle macromolecules and organelles. This pathway is activated under environmental stress conditions, during development and in various pathological situations. In this study, we describe the role of reactive oxygen species (ROS) as signaling molecules in starvation-induced autophagy. We show that starvation stimulates formation of ROS, specifically H2O2. These oxidative conditions are essential for autophagy, as treatment with antioxidative agents abolished the formation of autophagosomes and the consequent degradation of proteins. Furthermore, we identify the cysteine protease HsAtg4 as a direct target for oxidation by H2O2, and specify a cysteine residue located near the HsAtg4 catalytic site as a critical for this regulation. Expression of this regulatory mutant prevented the formation of autophagosomes in cells, thus providing a molecular mechanism for redox regulation of the autophagic process.