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Cysteine redox regulation of carbon metabolism in Arabidopsis thaliana
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International audience. A common occurrence of abio c and bio c stresses is the accumula on of reac ve oxygen species (ROS) which leads to oxida ve condi ons. ROS homeostasis is controlled through a complex network of ROS produc on and scavenging enzymes. One way for proteins to sense redox changes is through the reversible oxida on of cysteine thiol groups such as disulfide bond, S-nitrosyla on, S-glutathionyla on. These post-transla onal modifica ons of cysteines act as molecular switches altering protein ac vity, subcellular localiza on and binding affinity. Here, we describe how cysteines redox regula on influences the cellular carbon metabolism by regula ng key metabolic enzymes in the mitochondria and the cytosol (TCA cycle and associated enzymes) (1). We further decipher the redox regula on of two of these enzymes: cytosolic malate dehydrogenase (cMDH) and isocitrate dehydrogenase (cICDH) (2,3). Upon oxida ve condi ons, cMDH and cICDH undergo cysteine oxida on. On the one hand, cMDH1 experiences sulfur oxida on on specific cysteines and homodimerize through a C-terminal cysteine disulfide which protects cysteine (Cys330) from overoxida on. This inter-molecular disulfide forma on switches cMDH1 from a noncovalent homodimer to a disulfide-linked homodimer, affec ng the kine cs, the thermodynamic stability and represents an oxidized state which is reversible by thioredoxins (2). On the other hand, cICDH cysteines are prone to S-nitrosyla on and S-glutathionyla on. We show that a specific S-glutathionyla on on Cys363 inhibits cICDH ac vity, which is restored by glutaredoxins, sugges ng a redox regula on of cICDH by glutathionyla on (3). Metabolic enzyme ac vi es were studied in both ROS metabolism mutants (e.g. cat2) and in mutants affected in thiol reduc on systems, sugges ng a key role of the thiol reduc on systems to protect plant metabolism from oxida on (1, 2, 3). Therefore, we propose that the redox switch of different metabolic enzymes may contribute to adapt the cell metabolism to environmental constraints. (1) Daloso DM et al. (2015) Thioredoxin, a master regulator of the tricarboxylic acid cycle in plant mitochondria Proc. Natl. Acad. Sci. USA, 112(11):E1392-400. doi: 10.1073/pnas.1424840112. (2) Huang J, Niazi AK et al (2018) Self-protec on of Arabidopsis cytosolic malate dehydrogenase against oxida ve stress. J. Exp. Bot., 69(14):3491-3505. doi: 10.1093/jxb/erx396. (3) Niazi AK et al. (2019) Cytosolic Isocitrate Dehydrogenase is regulated by glutathionyla on in Arabidopsis thaliana. An oxidants. 2019 Jan 8;8(1). pii: E16. doi: 10.3390/an ox8010016.
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