Abscisic Acid-Triggered Persulfidation of the Cys Protease ATG4 Mediates Regulation of Autophagy by Sulfide
Abscisic Acid-Triggered Persulfidation of the Cys Protease ATG4 Mediates Regulation of Autophagy by Sulfide
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DOI：
10.1105/tpc.20.00766
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发表时间：
2020-12-01
期刊：
影响因子：
11.6
通讯作者：
Gotor, Cecilia
中科院分区：
文献类型：
--
作者：
Laureano-Marin, Ana M.;Aroca, Angeles;Gotor, Cecilia
硫化氢通过过硫化物修饰拟南芥AtATG 4a蛋白酶负调控自噬的进程。硫化氢是一种信号分子，调节植物中的重要过程，如自噬。在拟南芥（Arabidopsis thaliana）中，硫化氢通过一种未知的机制独立于活性氧负调控自噬。比较和定量蛋白质组学分析被用来检测脱落酸触发的过硫化，揭示了自噬相关（ATG）Cys蛋白酶AtATG 4a介导的自噬控制的主要作用。该蛋白酶经历Cys 170的特异性过硫化，Cys 170是Cys蛋白酶的特征性催化Cys-His-Asp三联体的一部分。使用莱茵衣藻CrATG 8蛋白作为底物，在异源测定中测试通过过硫化对ATG 4活性的调节。硫化物显著且可逆地使AtATG 4a失活。硫化物对ATG 4的可逆抑制的生物学意义得到了在拟南芥叶中在基础和自噬激活条件下获得的结果的支持。在氮饥饿和渗透胁迫下，拟南芥中的总体ATG 4蛋白水解活性显著增加，并且可以被硫化物抑制。因此，这些数据强烈表明硫化物对自噬的负调节是由ATG 4蛋白酶的特异性过硫化介导的。
Hydrogen sulfide negatively regulates the progress of autophagy through persulfide modification of the Arabidopsis AtATG4a protease.Hydrogen sulfide is a signaling molecule that regulates essential processes in plants, such as autophagy. In Arabidopsis (Arabidopsis thaliana), hydrogen sulfide negatively regulates autophagy independently of reactive oxygen species via an unknown mechanism. Comparative and quantitative proteomic analysis was used to detect abscisic acid-triggered persulfidation that reveals a main role in the control of autophagy mediated by the autophagy-related (ATG) Cys protease AtATG4a. This protease undergoes specific persulfidation of Cys170 that is a part of the characteristic catalytic Cys-His-Asp triad of Cys proteases. Regulation of the ATG4 activity by persulfidation was tested in a heterologous assay using the Chlamydomonas reinhardtii CrATG8 protein as a substrate. Sulfide significantly and reversibly inactivates AtATG4a. The biological significance of the reversible inhibition of the ATG4 by sulfide is supported by the results obtained in Arabidopsis leaves under basal and autophagy-activating conditions. A significant increase in the overall ATG4 proteolytic activity in Arabidopsis was detected under nitrogen starvation and osmotic stress and can be inhibited by sulfide. Therefore, the data strongly suggest that the negative regulation of autophagy by sulfide is mediated by specific persulfidation of the ATG4 protease.