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Spectrophotometric Screening for Potential Inhibitors of Cytosolic Glutathione S-Transferases
Published on: October 10, 2020
Mitochondrial glutathione transport: physiological, pathological and toxicological implications
1Department of Pharmacology, Wayne State University School of Medicine, 540 East Canfield Avenue, Detroit, MI 48201, USA. l.h.lash@wayne.edu <l.h.lash@wayne.edu>
Mitochondria contain a unique glutathione (GSH) pool transported from the cytoplasm via specific carriers. Enhancing dicarboxylate (DIC) and oxoglutarate (OGC) carrier expression protects cells from oxidative stress and apoptosis.
Area of Science:
- Cellular Biology
- Biochemistry
- Mitochondrial Physiology
Background:
- Most cellular glutathione (GSH) resides in the cytoplasm, but a distinct pool exists in mitochondria.
- Mitochondrial GSH must be transported from the cytoplasm, as GSH synthesis is primarily cytoplasmic.
- GSH is an anion at physiological pH, suggesting organic anion carriers facilitate its transport across the mitochondrial inner membrane.
Purpose of the Study:
- To investigate the specific carrier proteins responsible for transporting glutathione (GSH) into mitochondria.
- To explore the functional role of identified carriers in cellular protection against oxidative stress and apoptosis.
- To assess the implications of mitochondrial GSH transport for diseases associated with GSH depletion.
Main Methods:
- Utilized isolated mitochondria from rat kidney to study GSH transport mechanisms.
- Investigated the roles of the dicarboxylate carrier (DIC) and oxoglutarate carrier (OGC) in GSH transport.
- Employed overexpression of DIC and OGC cDNAs in NRK-52E cells to assess functional consequences.
Main Results:
- In rat kidney mitochondria, the dicarboxylate carrier (DIC) and oxoglutarate carrier (OGC) account for over 80% of GSH transport.
- The oxodicarboxylate carrier (ODC) has been identified but its role in GSH transport remains uninvestigated.
- Overexpression of DIC and OGC in NRK-52E cells conferred protection against oxidative stress and apoptosis.
Conclusions:
- DIC and OGC are key mediators of mitochondrial glutathione transport in kidney.
- Enhanced expression of these carriers offers a protective mechanism against cellular damage.
- Understanding mitochondrial GSH transport is crucial for developing therapies for diseases involving GSH depletion, such as liver and kidney diseases.
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