High-affinity transport of glutathione is part of a multicomponent system essential for mitochondrial function

Journal Article · Sat Sep 01 00:00:00 EDT 1990 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.87.18.7185· OSTI ID:5323748

Martensson, J; Lai, J C.K.; Meister, A ^[1]

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1. Cornell Univ., New York, NY (USA)

Glutathione, an essential cellular antioxidant required for mitochondrial function, is not synthesized by mitochondria but is imported from the cytosol. Rat liver mitochondria have a multicomponent system that underlies the remarkable ability of mitochondria to take up and retain glutathione. At external glutathione levels of <1 mM, glutathione is transported into the mitochondrial matrix by a high-affinity component which is saturated at levels of 1-2 mM and stimulated by ATP. Another component has lower affinity and is stimulated by ATP and ADP. Both components are inhibited by carbonylcyanide p-(trifuloromethoxy)phenylhydrazone (FCCP), glutamate, and ophthalmic acid. Increase of extramitochondrial glutathione promotes uptake and exchange; the intermembranous space seems to function as a recovery zone that promotes efficient recycling of matrix glutathione. The findings are in accord with in vivo data showing that (1) rapid exchange occurs between mitochondrial and cytosolic glutathione, (2) lowering of cytosolic glutathione levels (produced by administration of buthionine sulfoximine) decreases export of glutathione from mitochondria to cytosol, and (3) administration of glutathione esters increases glutathione levels in mitochondria more than those in the cytosol.

• OSTI ID: 5323748
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (United States) Vol. 87:18; ISSN 0027-8424; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
ANTIOXIDANTS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BODY
CELL CONSTITUENTS
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
DRUGS
EVEN-ODD NUCLEI
GLANDS
GLUTATHIONE
ISOTOPES
KINETICS
LABELLED COMPOUNDS
LIGHT NUCLEI
LIVER
MAMMALS
MEMBRANE PROTEINS
MEMBRANE TRANSPORT
MITOCHONDRIA
NUCLEI
ORGANIC COMPOUNDS
ORGANS
PEPTIDES
POLYPEPTIDES
PROTEINS
RADIOISOTOPES
RADIOPROTECTIVE SUBSTANCES
RATS
REACTION KINETICS
RODENTS
SULFUR 35
SULFUR ISOTOPES
VERTEBRATES