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Persulfidation of ATG18a regulates autophagy under ER stress in Arabidopsis.

Department of Genetics, Development and Cell Biology, Iowa State University, Ames, IA 50011; aaroca@us.es. Institute of Plant Biochemistry and Photosynthesis, Consejo Superior de Investigaciones Científicas, University of Seville, 41029 Seville, Spain. Consejo Superior de Investigaciones Científicas, Estación Experimental de Aula Dei, 50059 Zaragoza, Spain. Group of Biochemistry, Biophysics and Computational Biology, Consejo Superior de Investigaciones Científicas, University of Zaragoza, 50009 Zaragoza, Spain. Department of Genetics, Development and Cell Biology, Iowa State University, Ames, IA 50011.

Proceedings of the National Academy of Sciences of the United States of America. 2021;(20)
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Abstract

Hydrogen sulfide (H2S) is an endogenously generated gaseous signaling molecule, which recently has been implicated in autophagy regulation in both plants and mammals through persulfidation of specific targets. Persulfidation has been suggested as the molecular mechanism through which sulfide regulates autophagy in plant cells. ATG18a is a core autophagy component that is required for bulk autophagy and also for reticulophagy during endoplasmic reticulum (ER) stress. In this research, we revealed the role of sulfide in plant ER stress responses as a negative regulator of autophagy. We demonstrate that sulfide regulates ATG18a phospholipid-binding activity by reversible persulfidation at Cys103, and that this modification activates ATG18a binding capacity to specific phospholipids in a reversible manner. Our findings strongly suggest that persulfidation of ATG18a at C103 regulates autophagy under ER stress, and that the impairment of persulfidation affects both the number and size of autophagosomes.