Persulfidation of ATG18a regulates autophagy under ER stress inArabidopsis

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.

Protein Persulfidation in Plants: Function and Mechanism

“…Consistent with the conclusion of Laureano-Marín et al [90], Aroca et al reported that, under ER stress, the reversible persulfidation modification of ATG18a residue Cys103 enhanced its affinity and co-localization time with phagophore membranes (Table 1), thus delaying the release and maturation of autophagosomes [61]. However, when persulfidation was abolished, the size and number of autophagosomes were affected [61].…”

“…These proteins have a high degree of homology in animals, yeast and plants [80]. ATGs tightly regulate the process of autophagy and participate in the formation and release of autophagosomes, the fusion and enlargement of phospholipid membranes, and the size and number of autophagosomes [61,86,87]. Importantly, H 2 S might play an essential regulatory role in plant autophagy.…”

Plant Autophagy: An Intricate Process Controlled by Various Signaling Pathways

“…Recent studies have also deciphered the regulation of autophagosome biogenesis. For example, under ER stress, the phospholipid-binding activity of ATG18a can be activated by reversible persulfidation at Cys103 to negatively regulate autophagosome formation and ensure the appropriate physiological response ( Aroca et al, 2021 ). During nutrient starvation, coat protein complex II (COPII) vesicles act as a membrane source for autophagosome formation, mediated by the specific recognition of ATG8e by a COPII component, AtSar1d ( Zeng et al, 2021 ).…”

The Modus Operandi of Hydrogen Sulfide(H2S)-Dependent Protein Persulfidation in Higher Plants

“…These plant proteomic studies that identified potential protein targets of persulfidation were used as the starting point for complementary analyses to specifically identify the residue(s) persulfidated and to determine the effect of this oxiPTM on the function of the proteins targeted [ 40 ]. Table 1 [ 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 ] shows an updated list of the plant proteins undergoing persulfidation, and the effect on protein function. These persulfidated proteins are involved in a wide range of cellular processes, including photosynthesis, the sulfur metabolism, reactive oxygen/nitrogen species (ROS/RNS) activity, ethylene biosynthesis, organelle movements, autophagy and ABA signaling, thus confirming the important role of H 2 S in plant cell physiology.…”