S-D-Lactoylglutathione can be an alternative supply of mitochondrial glutathione

Armeni, Tatiana; Cianfruglia, Laura; Piva, Francesco; Urbanelli, Lorena; Caniglia, Maria Luisa; Pugnaloni, Armanda; Principato, Giovanni

doi:10.1016/j.freeradbiomed.2013.12.005

Cited by 46 publications

(45 citation statements)

References 49 publications

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“…On the other hand, a recent alternative way for supplying the mitochondrial pool of GSH (mtGSH) has been described by our group. Our studies demonstrated that S‐D‐lactoylglutathione, a thioester of glutathione and an intermediate of the glyoxalase system, enters mitochondria to undergo Glx‐II mediated hydrolysis to D‐lactate and GSH that is then available to restore the mtGSH pool .…”

Section: Subcellular Compartmentalizationmentioning

confidence: 78%

Glutathione compartmentalization and its role in glutathionylation and other regulatory processes of cellular pathways

et al. 2018

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Glutathione is considered the major non‐protein low molecular weight modulator of redox processes and the most important thiol reducing agent of the cell. The biosynthesis of glutathione occurs in the cytosol from its constituent amino acids, but this tripeptide is also present in the most important cellular districts, such as mitochondria, nucleus, and endoplasmic reticulum, thus playing a central role in several metabolic pathways and cytoprotection mechanisms. Indeed, glutathione is involved in the modulation of various cellular processes and, not by chance, it is a ubiquitous determinant for redox signaling, xenobiotic detoxification, and regulation of cell cycle and death programs. The balance between its concentration and redox state is due to a complex series of interactions between biosynthesis, utilization, degradation, and transport. All these factors are of great importance to understand the significance of cellular redox balance and its relationship with physiological responses and pathological conditions. The purpose of this review is to give an overview on glutathione cellular compartmentalization. Information on its subcellular distribution provides a deeper understanding of glutathione‐dependent processes and reflects the importance of compartmentalization in the regulation of specific cellular pathways. © 2018 BioFactors, 45(2):152–168, 2019

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Section: Subcellular Compartmentalizationmentioning

confidence: 78%

Glutathione compartmentalization and its role in glutathionylation and other regulatory processes of cellular pathways

et al. 2018

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“…44,45 These proteins are also involved in many diseases, such as Friedreich ataxia for actin and cardiovascular diseases for MDH. [46][47][48] Actin and MDH are already known to undergo S-glutathionylation as posttranslational modifications, [49][50][51] but the possible Sglutathionylation by Glo2 in different cellular compartments (cytosol and mitochondria) 52,53 is interesting because it could be considered as a new catalyst of S-glutathionylation, besides its known role as a thioester hydrolase in 2-oxoaldehydes detoxification. 54 In fact, as shown by our results, Glo2 plus its substrate SLG seem to induce an enzymatic glutathionylation of MDH and actin and, as detected for MDH, also alter the conformation of the target protein modifying its activity.…”

Section: Discussionmentioning

confidence: 99%

“…In a previous study by our group, we showed in fact that SLG can enter into mitochondria where it can be hydrolyzed by mitochondrial Glo2 to produce D-Lactic acid and GSH. 52,55 In this perspective, Glo2 can play a new important regulatory role in Sglutathionylation, acquiring further significance in cellular post-translational modifications of proteins.…”

Section: Discussionmentioning

confidence: 99%

A possible S‐glutathionylation of specific proteins by glyoxalase II: An in vitro and in silico study

Ercolani

Scirè

Galeazzi

et al. 2016

Cell Biochemistry & Function

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This article reports for the first time a possible additional role of Glo2 that, after interacting with a target protein, is able to promote S-glutathionylation using its natural substrate SLG, a glutathione derived compound. In this perspective, Glo2 can play a new important regulatory role inS-glutathionylation, acquiring further significance in cellular post-translational modifications of proteins.

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“…In addition to the ability of mitochondrial-permeable GSH-EE to directly increase mGSH levels bypassing the mitochondrial transport defect, it has been recently described additional strategies that supply mitochondria with GSH, including parental molecules that generate GSH once inside the mitochondrial matrix. This approach has been recently illustrated with the use of S - D -lactoylglutathione (Armeni et al, 2014). This compound is an intermediate of the glyoxalase system, which is hydrolyzed in the mitochondrial matrix yielding lactate and GSH; hence showing the ability to replenish mGSH resulting in recovery of mitochondrial function and antioxidant defense.…”

Section: Conclusion and Future Approachesmentioning

confidence: 99%

Glutathione and mitochondria

2014

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Glutathione (GSH) is the main non-protein thiol in cells whose functions are dependent on the redox-active thiol of its cysteine moiety that serves as a cofactor for a number of antioxidant and detoxifying enzymes. While synthesized exclusively in the cytosol from its constituent amino acids, GSH is distributed in different compartments, including mitochondria where its concentration in the matrix equals that of the cytosol. This feature and its negative charge at physiological pH imply the existence of specific carriers to import GSH from the cytosol to the mitochondrial matrix, where it plays a key role in defense against respiration-induced reactive oxygen species and in the detoxification of lipid hydroperoxides and electrophiles. Moreover, as mitochondria play a central strategic role in the activation and mode of cell death, mitochondrial GSH has been shown to critically regulate the level of sensitization to secondary hits that induce mitochondrial membrane permeabilization and release of proteins confined in the intermembrane space that once in the cytosol engage the molecular machinery of cell death. In this review, we summarize recent data on the regulation of mitochondrial GSH and its role in cell death and prevalent human diseases, such as cancer, fatty liver disease, and Alzheimer’s disease.

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S-D-Lactoylglutathione can be an alternative supply of mitochondrial glutathione

Cited by 46 publications

References 49 publications

Glutathione compartmentalization and its role in glutathionylation and other regulatory processes of cellular pathways

Glutathione compartmentalization and its role in glutathionylation and other regulatory processes of cellular pathways

A possible S‐glutathionylation of specific proteins by glyoxalase II: An in vitro and in silico study

Glutathione and mitochondria

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