Corpus ID: 452853

Evidence for mitochondrial uptake of glutathione by dicarboxylate and 2-oxoglutarate carriers.

@article{Chen1998EvidenceFM,
  title={Evidence for mitochondrial uptake of glutathione by dicarboxylate and 2-oxoglutarate carriers.},
  author={Z Chen and Lawrence H. Lash},
  journal={The Journal of pharmacology and experimental therapeutics},
  year={1998},
  volume={285 2},
  pages={
          608-18
        }
}
  • Z. Chen, L. Lash
  • Published 1 May 1998
  • Chemistry, Medicine
  • The Journal of pharmacology and experimental therapeutics
The role of organic anion transporters in the mitochondrial uptake of glutathione (GSH) was investigated by assessing competition with substrates or inhibition with inhibitors of specific carriers and modulation of mitochondrial energetics. Potential artifacts in the transport methodology, including contamination of matrix space with extramitochondrial fluid, changes in matrix volume during incubations, efflux of transported GSH during sample processing, induction of the membrane permeability… Expand
Mitochondrial glutathione transport: physiological, pathological and toxicological implications.
  • L. Lash
  • Biology, Medicine
  • Chemico-biological interactions
  • 2006
TLDR
Overexpression of the cDNA for the DIC and OGC in a renal proximal tubule-derived cell line showed that enhanced carrier expression and activity protects against oxidative stress and chemically induced apoptosis, having implications for development of novel therapeutic approaches for treatment of human diseases and pathological states. Expand
Hepatic mitochondrial transport of glutathione: studies in isolated rat liver mitochondria and H4IIE rat hepatoma cells.
TLDR
H4IIE cells, a rat hepatoma cell line, were stably transfected with the cDNA for the OGC, and exhibited increased uptake of GSH and 2-oxoglutarate and were protected from cytotoxicity induced by H(2)O(2), methyl vinyl ketone, or cisplatin, demonstrating the protective function of increased mitochondrial GSH transport in the liver. Expand
Enrichment and functional reconstitution of glutathione transport activity from rabbit kidney mitochondria: further evidence for the role of the dicarboxylate and 2-oxoglutarate carriers in mitochondrial glutathione transport.
TLDR
GSH transport activity was enriched from rabbit kidney mitochondria and functionally reconstituted into phospholipid vesicles and suggested that the dicarboxylate carrier contributes a somewhat higher proportion to overall GSH uptake and that both carriers account for 70 to 80% of total G SH uptake. Expand
Sensitivity of the 2‐oxoglutarate carrier to alcohol intake contributes to mitochondrial glutathione depletion
TLDR
Findings provide unequivocal evidence for 2‐oxoglutarate as a GSH carrier and its sensitivity to membrane dynamics perturbation contributes in part to the alcohol‐induced mGSH depletion. Expand
Dicarboxylate carrier-mediated glutathione transport is essential for reactive oxygen species homeostasis and normal respiration in rat brain mitochondria.
TLDR
It is suggested that DIC is the main glutathione transporter in cortical mitochondria and that Dicarboxylate transport is essential for these mitochondria to maintain ROS homeostasis and normal respiratory functions. Expand
Mitochondrial glutathione in toxicology and disease of the kidneys
TLDR
Genetic manipulation of DIC and/or OGC expression in renal cell lines demonstrated the ability to produce sustained increases in mitochondrial GSH content, which protected these cells from cytotoxicity due to several oxidants and mitochondrial toxicants. Expand
Cellular and subcellular heterogeneity of glutathione metabolism and transport in rat kidney cells.
TLDR
It is shown that mitochondria from DT cells have a significantly lower capacity to use GSH for detoxification and regulation of redox status. Expand
Hepatic mitochondrial glutathione: transport and role in disease and toxicity.
TLDR
Evidence mainly from kidney and liver mitochondria indicated that the dicarboxylate and the 2-oxoglutarate carriers contribute to the transport of GSH across the mitochondrial inner membrane, however, differential features between kidneys and liver mitochondrial GSH transport seem to suggest the existence of additional carriers the identity of which remains to be established. Expand
S-D-Lactoylglutathione can be an alternative supply of mitochondrial glutathione.
TLDR
This work found that SLG (S-D-lactoylglutathione), an intermediate of the glyoxalase system, can enter the mitochondria and there be hydrolyzed from mitochondrial gly oxalase II enzyme to D- lactate and GSH, and showed new alternative sources of GSH supply to the mitochondaria by SLG. Expand
Modulation of Expression of Rat Mitochondrial 2-Oxoglutarate Carrier in NRK-52E Cells Alters Mitochondrial Transport and Accumulation of Glutathione and Susceptibility to Chemically Induced Apoptosis
TLDR
Results provide further evidence that genetic manipulation of mitochondrial GSH transporter expression alters mitochondrial and cellular GSH status, resulting in markedly altered susceptibility to chemically induced apoptosis. Expand
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References

SHOWING 1-10 OF 42 REFERENCES
Evidence That the Rat Hepatic Mitochondrial Carrier Is Distinct from the Sinusoidal and Canalicular Transporters for Reduced Glutathione
TLDR
The results show the successful expression of the rat hepatic mitochondrial GSH carrier, which is different from RsGshT and RcGShT, and provide the strategic basis for the cloning of this important carrier. Expand
Uptake of glutathione by renal cortical mitochondria.
TLDR
Results demonstrate uptake of GSH into renal cortical mitochondria that appears to involve electroneutral countertransport (exchange) with other dicarboxylates, and Functionally, GSH uptake into mitochondria can protect these organelles from various forms of injury, such as oxidative stress. Expand
The role of glutathione in the retention of Ca2+ by liver mitochondria.
TLDR
It is proposed that the GSSG/GSH ratio, by controlling the reduction state of critical sulfhydryl groups, regulates lysophospholipid acyltransferase activity and, therefore, the ability of mitochondria to remain impermeable upon activation of the intramitochondrial Ca2+ requiring phospholipase A2. Expand
High-affinity transport of glutathione is part of a multicomponent system essential for mitochondrial function.
TLDR
The intermembranous space seems to function as a recovery zone that promotes efficient recycling of matrix glutathione in mitochondria, in accord with in vivo data showing that rapid exchange occurs between mitochondrial and cytosolic glutATHione. Expand
Intracellular distribution of thiols and disulfides: assay of mitochondrial glutathione transport.
  • L. Lash
  • Biology, Medicine
  • Methods in enzymology
  • 1995
TLDR
Methods to quantify transport of glutathione (GSH) as the intact tripeptide into rat renal mitochondria are described, although the methods are applicable to measurement of transport into mitochondria from other tissues with appropriate, minor modifications. Expand
Relationships between the NAD(P) redox state, fatty acid oxidation, and inner membrane permeability in rat liver mitochondria.
TLDR
It has been shown that the ADP/ATP carrier adopts the c-state conformation (i.e., nucleotide binding site facing the cytoplasm) during fatty acid oxidation, which can partially protect the membrane structure after energization. Expand
Status of the mitochondrial pool of glutathione in the isolated hepatocyte.
TLDR
Using the selective membrane-solubilizing properties of digitonin and a rapid centrifugation method to separate cytoplasmic and mitochondrial components, the metabolic state of mitochondrial glutathione was investigated in isolated rat hepatocytes and demonstrated that in the absence of label reincorporation, liver glutATHione exhibits a biphasic turnover. Expand
Selective depletion of mitochondrial glutathione concentrations by (R,S)-3-hydroxy-4-pentenoate potentiates oxidative cell death.
TLDR
The critical role of mitochondrial glutathione in cytoprotection is established and (R,S)-3-hydroxy-4-pentenoate may find utility in exploring mitochondrial glutATHione homeostasis. Expand
The mitochondrial pyruvate carrier. Kinetics and specificity for substrates and inhibitors.
TLDR
The possibility that pyruvate transport into mitochondria may be rate limiting and involved in the regulation of gluconegenesis is discussed, and alpha-cyano-4-hydroxycinnamate was shown to be accompanied by the transport of a proton (or by exchange with an OH-ion), which allowed measurements of pyruVate transport at higher temperatures to be made. Expand
Direct evidence for the role of the membrane potential in glutathione transport by renal brush-border membranes.
TLDR
GSH which is secreted into the tubular lumen by a specific translocase in the lumenal membranes or filtered by the glomerulus may be degraded in situ by membranous gamma-glutamyltransferase and peptidase activities which hydrolyze peptide bonds of cysteinylglycine and its derivatives. Expand
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