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News | Photosynthesis | Toxicology | Microalgae
A team from I2BC (SB2SM) used a combination of in vitro and in vivo approaches in the model cyanobacterium Synechocystis to establish a logical, but as yet never described, link between the detoxification of methylglyoxal, a toxic metabolite, and glutathione S-transferase, an enzyme of the xenobiotic metabolism, conserved during evolution.
Methylglyoxal (MG) is a detrimental metabolic by-product that threatens most organisms. In humans, MG can cause diabetes and neurodegeneratives diseases. It strongly interacts with lipids, nucleic acids, and the lysine and arginine residues of proteins, generating advanced glycation end products (AGEs) that disturb cell metabolism. MG is predominantly detoxified by the glyoxalase pathway. This process begins with the conjugation of MG with glutathione (GSH), supposed to be non-enzymatic, yielding a hemithioacetal product that is subsequently transformed by the glyoxalase enzymes into D-lactate and GSH.
MG has been overlooked in photosynthetic organisms, although they inevitably produce it not only by the catabolism of sugars, lipids, and amino acids, as do heterotrophic organisms, but also by their active photoautotrophic metabolism. This is especially true for cyanobacteria that are regarded as having developed photosynthesis and GSH-dependent enzymes to detoxify the reactive oxygen species produced by their photosynthesis (CO2 assimilation) and respiration (glucose catabolism), which they perform in the same cell compartment.
In this study, researchers show for the first time that the Sll0067 glutathione transferase (GST) of the model cyanobacterium Synechocystis sp. strain PCC 6803 plays a prominent role in MG tolerance and detoxification, unlike the other five GSTs of this organism. Sll0067 catalyzes the conjugation of MG with GSH to initiate its elimination driven by glyoxalases. These results are novel because the conjugation of MG with GSH is always described as nonenzymatic. They will certainly stimulate the analysis of Sll0067 orthologs from other organisms with possible impacts on human health (development of biomarkers or drugs) and/or agriculture.
See also : From bacteria to Humans: characterization of a new player in tolerance to thermal and oxidative stress.
X. Kammerscheit, A. Hecker, N. Rouhier, F. Chauvat, C. Cassier-Chauvat. Methylglyoxal Detoxification Revisited: Role of Glutathione Transferase in Model Cyanobacterium Synechocystis sp. Strain PCC 6803. mBio, 2020, 11:e00882-20. https://mbio.asm.org/content/11/4/e00882-20/article-info
CEA is a French government-funded technological research organisation in four main areas: low-carbon energies, defense and security, information technologies and health technologies. A prominent player in the European Research Area, it is involved in setting up collaborative projects with many partners around the world.