Hepatic mitochondrial glutathione: transport and role in disease and toxicity
- Liver Unit, Hospital Clinic I Provincial, Instituto Investigaciones Biomedicas August Pi i Sunyer (Spain) and Departamento de Patologia Experimental, Instituto Investigaciones Biomedicas de Barcelona, Consejo Superior Investigaciones Cientificas (Spain)
- Department of Medicine, Keck School of Medicine, University of Southern California, USC Research Center for Alcoholic Liver and Pancreatic Diseases, Los Angeles, CA 90007 (United States)
Synthesized in the cytosol of cells, a fraction of cytosolic glutathione (GSH) is then transported into the mitochondrial matrix where it reaches a high concentration and plays a critical role in defending mitochondria against oxidants and electrophiles. 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 kidney and liver mitochondrial GSH (mGSH) transport seem to suggest the existence of additional carriers the identity of which remains to be established. One of the characteristic features of the hepatic mitochondrial transport of GSH is its regulation by membrane fluidity. Conditions leading to increased cholesterol deposition in the mitochondrial inner membrane such as in alcohol-induced liver injury decrease membrane fluidity and impair the mitochondrial transport of GSH. Depletion of mitochondrial GSH by alcohol is believed to contribute to the sensitization of the liver to alcohol-induced injury through tumor necrosis factor (TNF)-mediated hepatocellular death. Through control of mitochondrial electron transport chain-generated oxidants, mitochondrial GSH modulates cell death and hence its regulation may be a key target to influence disease progression and drug-induced cell death.
- OSTI ID:
- 20721794
- Journal Information:
- Toxicology and Applied Pharmacology, Vol. 204, Issue 3; Other Information: DOI: 10.1016/j.taap.2004.10.001; PII: S0041-008X(04)00457-0; Copyright (c) 2004 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0041-008X
- Country of Publication:
- United States
- Language:
- English
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