Biochimica et Biophysica Acta (BBA) - General Subjects
Review
Glutathione transporters☆
Highlights
► Glutathione transporters described in different organisms and different organelles. ► Eukaryotic cells have multiple glutathione transporters. ► Glutathione transporters have evolved from different protein families. ► Low and high affinity transporters are described. ► Yeast high affinity transporters have facilitated structure function studies.
Section snippets
Introduction and historical perspective
Glutathione (GSH) is the most abundant small molecular weight thiol present in living cells. It is synthesized in the cytoplasm (although in plants part of the synthesis is in the chloroplasts) [1], but carries out a variety of functions both in the cytoplasm and other organelles. The roles of glutathione include its role as a redox buffer [2], [3], [4], in the cellular response to oxidative stress, biosynthesis of iron–sulfur proteins in the mitochondria [5], [6], [7], [8], detoxification of
The yeast high affinity glutathione transporters are members of the oligopeptide transporter family
Biochemical studies with yeasts had revealed the presence of glutathione uptake systems in S. cerevisiae [14]. Subsequent studies with this yeast led to the identification of the first high affinity glutathione transporter, Hgt1p [38] that was required for the uptake of glutathione from the extracellular medium. Deleting the gene for this transporter led to an almost complete loss in uptake of radioactive glutathione. Knockout of the gene was also synthetically lethal with a knockout of the
The MRP/CFTR family in low affinity glutathione efflux
The multidrug resistance associated protein (MRP) family is a subclass of the ABC superfamily (ABCC). In humans, this family includes a total of nine MRP genes (MRP1 to MRP9) and the cystic fibrosis transmembrane regulator (CFTR). These proteins are plasma membrane localized. ATP-binding and hydrolysis provide the driving force for pumping substrates out of the cell. These proteins are known to be involved in multidrug resistance and function as multispecific organic anion transporters, but
Concluding remarks
Glutathione transporters play a key role in glutathione homeostasis of living cells. Despite their importance, the identification and characterization of glutathione transporters have been difficult, progress slow, and at times controversial. The differing requirements in the cell and the organelles have led to the evolution of glutathione transporters from different protein families with widely differing kinetic parameters, and substrate specificities. Some of the glutathione transporters such
Acknowledgements
AT and MZ acknowledge receipt of fellowship from CSIR, India. This work was supported in part by Grant-in-Aid projects to A.K.B. from the Departments of Science and Technology and Department of Biotechnology, Government of India.
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This article is part of a Special Issue entitled Cellular functions of glutathione.