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Conrad, M. ; Sato, H.*

The oxidative stress-inducible cystine/glutamate antiporter, system xc-: Cystine supplier and beyond.

Amino Acids 42, 231-246 (2012)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
The oxidative stress-inducible cystine/glutamate exchange system, system x (c) (-) , transports one molecule of cystine, the oxidized form of cysteine, into cells and thereby releases one molecule of glutamate into the extracellular space. It consists of two protein components, the 4F2 heavy chain, necessary for membrane location of the heterodimer, and the xCT protein, responsible for transport activity. Previously, system x (c) (-) has been regarded to be a mere supplier of cysteine to cells for the synthesis of proteins and the antioxidant glutathione (GSH). In that sense, oxygen, electrophilic agents, and bacterial lipopolysaccharide trigger xCT expression to accommodate with increased oxidative stress by stimulating GSH biosynthesis. However, emerging evidence established that system x (c) (-) may act on its own as a GSH-independent redox system by sustaining a redox cycle over the plasma membrane. Hallmarks of this cycle are cystine uptake, intracellular reduction to cysteine and secretion of the surplus of cysteine into the extracellular space. Consequently, increased levels of extracellular cysteine provide a reducing microenvironment required for proper cell signaling and communication, e.g. as already shown for the mechanism of T cell activation. By contrast, the enhanced release of glutamate in exchange with cystine may trigger neurodegeneration due to glutamate-induced cytotoxic processes. This review aims to provide a comprehensive picture from the early days of system x (c) (-) research up to now.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords 4F2; Cystine/cysteine redox cycle; Glutamate; Glutathione; Slc7a11; xCT
ISSN (print) / ISBN 0939-4451
e-ISSN 1438-2199
Journal Amino Acids
Quellenangaben Volume: 42, Issue: 1, Pages: 231-246 Article Number: , Supplement: ,
Publisher Springer
Publishing Place Wien, Austria
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Developmental Genetics (IDG)