PT - JOURNAL ARTICLE AU - Laureano-Marín, Ana M. AU - Aroca, Ángeles AU - Pérez-Pérez, M. Esther AU - Yruela, Inmaculada AU - Jurado-Flores, Ana AU - Moreno, Inmaculada AU - Crespo, José L. AU - Romero, Luis C. AU - Gotor, Cecilia TI - Abscisic Acid-Triggered Persulfidation of the Cys Protease ATG4 Mediates Regulation of Autophagy by Sulfide AID - 10.1105/tpc.20.00766 DP - 2020 Dec 01 TA - The Plant Cell PG - 3902--3920 VI - 32 IP - 12 4099 - http://www.plantcell.org/content/32/12/3902.short 4100 - http://www.plantcell.org/content/32/12/3902.full SO - Plant Cell2020 Dec 01; 32 AB - 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.