Control of cellular damage: dissecting the physiological functions of the glyoxalase system in plants

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Reactive carbonyl species (RCS) are highly reactive small electrophilic mono- and di-carbonyl molecules formed during cellular metabolism. In humans, RCS are involved in several degenerative processes and diseases. In plants, the most abundant RCS are glyoxal (GO) and methylglyoxal (MGO), whose formation is closely connected to the fluxes through glycolysis and the Calvin-Benson cycle. RCS accumulate in plant tissues upon exposure to various abiotic stresses such as salinity, drought, and cold. This connection has prompted intense research on strategies for the enhancement of plant fitness and yield through RCS scavenging systems. The main pathway to detoxify GO and MGO is the glyoxalase (GLX) system, which consists of two enzymes, S-D-lactoylglutathione lyase (glyoxalase I, GLXI) and S-2-hydroxyacylglutathione hydrolase (glyoxalase II, GLXII), acting in sequence. Plants possess also GLXI-like proteins, which, together with the GLXI proteins, belong to the vicinal oxygen chelate superfamily. Our previous work suggests that (i) a specific group of GLXI proteins are unique to the Viridiplantae and likely co-evolved with a cluster of Viridiplantae-specific GLXII proteins; and (ii) Arabidopsis GLXI isoforms seem to act in vivo on different RCS with different specificity. In this proposal, we aim to clarify the participation of different GLXI and GLXII activities in the control of cellular damage by different RCS. To achieve this aim, we propose to follow complementary approaches, including (i) the functional characterization of plant lines with modified expression of specific GLXI and GLXII isoforms; (ii) the biochemical characterization of recombinant GLXI; (iii) the use of untargeted metabolomics to pursue the identification of additional substrates of the GLXI isoforms; and (iv) to use complementary protein-protein interaction approaches to analyse if GLXI and GLXII isoforms physically interact to efficiently channel the intermediates of the reactions.