SSHelectPhagy · Regulation of Selective autophagy by sulfide through persulfidation of protein targets.
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2019-06-15 → 2021-06-14
- EU contribution
- €175,099
- Participants
- 2
- Scheme
- MSCA-IF-GF
Lines connect the coordinator with its partners.
Results in brief
Regulation of Selective autophagy by sulfide through persulfidation of protein targets.
The overall aim of this project was to shed light to the role of sulfide in the regulation of selective autophagy of ER and Mitophagy, through persulfidation, and to broaden the range of plant targets for reticulophagy and mitophagy that are signaled by sulfide. ATG18a was found to be persulfidated in Arabidopsis under physiological conditions but the role of its persulfidation in autophagy has not been studied. We therefore hypothesized that persulfidation of ATG18a regulates ER stress–induced autophagy in Arabidopsis. To test this hypothesis, we proposed the following objectives: O1.1. Study the role of sulfide in ER stress. Functional analysis of ATG18a in vitro. O1.2. Study of the physiological effects of sulfide under ER stress conditions in Arabidopsis. O1.3. Functional analysis of persulfidation of ATG18a in ER stress. The overall aim of the second part of this project was to shed light to the regulation of mitophagy by sulfide and identify new receptors regulated by persulfidation. We therefore hypothesized that sulfide regulates mitophagy in Arabidopsis. To test this hypothesis, we proposed the following objectives: O2.1 Determine the role of sulfide treatments in mitophagy regulation O2.2 Isolation and identification of Persulfidated targets during mitophagy. O2.3. Functional characterization of persulfidated targets. Autophagy is a conserved degradative process in eucaryotes that serves as a recycling process for misfolded proteins or unfunctional organelles. The research carried out in this project has allowed us to advance in the knowledge of the regulatory mechanisms of autophagy under ER stress. Hydrogen sulfide has been proposed as a regulatory molecule of autophagy, but these results are pioneer in deciphering its way of action through the modification of ATG18a by persulfidation, an autophagy core machinery protein. It has been also demonstrated the effect of sulfide as a negative regulator of mitophagy. The research developed may have an impact on improvement of crop productivity and adaptation mechanisms of plants against adverse environmental conditions.
Data: CORDIS, © European Union
Project objective
The researcher will address the contribution of sulfide to regulation of selective autophagy in plants through persulfidation. This fellowship will be carried out at Iowa State University under the supervision of Prof. Bassham. The researcher will return to the European host, the University of Seville for 12 months under the supervision of Dr.Gotor at the Institute of Plant Biochemistry and Photosynthesis (IBVF). This project aims at understanding of selective autophagy regulation by sulfide in plants. Autophagy has conserved functions in development, cellular homeostasis, and stress responses from yeast to plants and mammals. In plants, autophagy is critically important in many aspects of plant life, including seedling establishment, plant development, stress resistance, metabolism and reproduction. It contributes to intracellular homeostasis in cells by selectively degrading aggregated proteins, damaged mitochondria, ribosomes, toxic macromolecules, and pathogens to prevent toxicity. This selective autophagy is mediated by the binding of adaptor proteins, which links a cargo targeted for degradation to the autophagosome machinery. An increasing number of targets for selective autophagy under different stress conditions have emerged in recent years, but the underlying mechanisms of their regulation are still so far unknown. Hydrogen sulfide (H2S) acts as an inhibitor of autophagy induced by nutrient deprivation and its mechanism has been proposed to be through persulfidation of specific targets. Several autophagy (ATG)-related proteins have been identified as modified by persulfidation in previous studies. The overall aim of this project is to shed light to the role of sulfide in the regulation of selective autophagy, mainly of mitochondria and ER, through persulfidation, and to broaden the range of plant targets for mitophagy and reticulophagy that are signaled by sulfide.
Original text from CORDIS.
Participants
- UNIVERSIDAD DE SEVILLA · SevillaCoordinatorSpain
- IOWA STATE UNIVERSITY OF SCIENCE AND TECHNOLOGY · AmesUnited States
Links
Data: CORDIS, © European Union