Cellular Compartmentalization, Glutathione Transport and Its Relevance in Some Pathologies

Abstract

Reduced glutathione (GSH) is the most abundant non-protein endogenous thiol. It is a ubiquitous molecule produced in most organs, but its synthesis is predominantly in the liver, the tissue in charge of storing and distributing it. GSH is involved in the detoxification of free radicals, peroxides and xenobiotics (drugs, pollutants, carcinogens, etc.), protects biological membranes from lipid peroxidation, and is an important regulator of cell homeostasis, since it participates in signaling redox, regulation of the synthesis and degradation of proteins (S-glutathionylation), signal transduction, various apoptotic processes, gene expression, cell proliferation, DNA and RNA synthesis, etc. GSH transport is a vital step in cellular homeostasis supported by the liver through providing extrahepatic organs (such as the kidney, lung, intestine, and brain, among others) with the said antioxidant. The wide range of functions within the cell in which glutathione is involved shows that glutathione’s role in cellular homeostasis goes beyond being a simple antioxidant agent; therefore, the importance of this tripeptide needs to be reassessed from a broader metabolic perspective.

Glutathione accelerates the cell cycle and cellular reprogramming in plant regeneration

“…There are circumstances in both plant and animal systems where GSH is imported into the nucleus. In animals, GSH is imported into the nucleus through Bcl2-associated athanogene pores [46], but the Bcl-2 gene is not conserved in plants. We demonstrate in this work that GSH is enriched in G1 nuclei in vivo and that G1 nuclei more quickly import free GSH than nuclei in cells in other phases of the cell cycle.…”

Polymersomes as Innovative, Stimuli-Responsive Platforms for Cancer Therapy

“…This degradation is largely attributed to the elevated concentrations of GSH in intracellular compartments (such as the cytosol, mitochondria, and cell nucleus) in comparison to extracellular fluids [ 99 ]. The intracellular environment, characterized by a significant reducing capacity due to the predominant localization of GSH (85–90%) in the cytosol relative to other organelles (which contain only 10–15% of GSH) [ 113 ], establishes a concentration gradient that is critical for the development of reduction-responsive polymersomes with disulfide bonds, thereby enabling targeted drug delivery to specific sites of action [ 113 ].…”

Unraveling the Multifaceted Role of Glutathione in Sepsis: A Comprehensive Review

“…Over 90% of cellular glutathione is found in its reduced form (GSH), with the remaining portion in the oxidized form (GSSG). However, the systemic availability of orally ingested glutathione is constrained due to poor bioavailability [ 5 ].…”