LAUSR

The superfamily of glutathione transferases (GSTs) comprises several distinct and multifunctional proteins widely distributed in Nature among eukaryotes and prokaryotes. GSTs are divided according to their cellular localization, with the cytosolic GSTs largely distributed in eukaryotes and further subgrouped into seven distinct classes of enzymes (Mannervik et al., 2005; Board and Menon, 2013). Besides the early recognized involvement of GSTs in the metabolism of drugs and xenobiotics, a growing number of data has revealed other biological functions of GSTs. These include isomerase reactions, protein glutathionylation, and the regulation of signaling pathways (Board and Menon, 2013). Non-enzymatic functions, including the regulation of the MAPK pathway (Adler et al., 1999; Pljesa-Ercegovac et al., 2018) and ryanodine receptors (Dulhunty et al., 2011), have also been proposed for some GSTs. During recent years, the interest in GSTs has increased due to their involvement in varied fields of biology and medicine. Moreover, the development of specific GST inhibitors has become an active topic of study. The reviews and research articles of the present Research Topic represent an attempt to focus on the novel, not yet fully explored mechanisms and functions of GSTs. Mannervik and colleagues review the ketosteroid isomerase activity of GSTs in the first manuscript of this research topic. The authors summarize and discuss studies about the contribution of alpha-class GSTs (GSTA) to steroid hormone biosynthesis in mammalian tissues. Human GSTA3-3 and GSTA1-1 isoforms support the activity of the 3β-hydroxysteroid dehydrogenase, which catalyzes the steroid isomerization to produce progesterone and 4androstenedione from their delta 5-precursors. GSTA3-3 plays the highest ketosteroid isomerase activity in human and equine steroidogenic tissues. The mechanism involving the thiolate of glutathione (GSH), the mammalian orthologs of GSTA3-3, the available structural analysis, and the substrate selectivity are discussed. Altogether, this manuscript exemplifies how GSTs acquired novel functions in steroid biochemistry. The following two papers are dedicated to GST polymorphisms and their significance in lung inflammation. This is a very active field of research with many possible pathophysiological implications related to the different functions of GSTs. Besides the classical reactions of detoxification catalyzed by GSTs against harmful environmental compounds, their regulatory functions on intracellular inflammatory signaling are considered here (Menon et al., 2015; Menon et al., 2017; Hughes et al., 2019). GST polymorphisms were also correlated with the increased risk of developing chronic inflammatory lung diseases (Ishii et al., 1999; Yanbaeva et al., 2009; Piacentini et al., 2013; Piaggi et al., 2021; van deWetering et al., 2021). The review by OPEN ACCESS