xCT

xCT is a sodium independent glutamate transporter that regulates the exchange of extracellular l-cystine and intracellular l-glutamate across the plasma membrane. This process is critical to glutathione production and protection from subsequent oxidative stress.

xCT is an obligate, electroneutral, membrane-bound anionic transporter responsible for regulating particular amino acid gradients via their transport through plasma membrane. The antiporter xCT superficially resembles an ion channel and preferentially catalyzes the exchange of L-cystine for L-glutamate residues in animal cells. Unlike other glutamate transporters like EAATs, xCT functions independently of an electrochemical sodium ion gradient. xCT is present in most peripheral tissues (heart, bone, liver, and testes).

xCT, encoded by the gene SLC7A11, is a member of the heterodimeric amino acid transporter family. Proteins within this family are linked to one another via a disulphide bond to form heterodimers consisting of one light subunit and one heavy subunit (1). These heterodimers facilitate the transport of amino acids across cell membranes. The light subunit xCT dimerises with the heavy subunit 4F2hc and the role of the xCT-4F2hc heterodimer, also known as system Xc-, is to couple the release of one molecule of intracellular glutamate to the uptake of one molecule of extracellular cystine (2).

There are two opposing sides to the controversial cysteine/glutamate antiporter. On one hand, it can be viewed a guardian of the cell, protecting it from the damaging oxidative stress that can cause cell death and even cancer. But, conversely, it has a dark side, actually facilitating cancer in a number of ways.

Glutathione, called GSH in its reduced form and GSSG or L(-)-Glutathione in its oxidized form, is an endogenous antioxidant found in most cells in the body.