Solute carrier family 7 member 11 (SLC7A11) (SLC7A11)

The Plasma cystine / cellular cysteine–glutathione synthesis system is a coordinated biochemical pathway essential for maintaining cellular redox homeostasis and preventing oxidative damage (Koppula et al., 2021, PubMed 31439724). The system begins with the uptake of extracellular cystine via the cystine/glutamate transporter (System xC-), which is a heterodimer consisting of the Solute carrier family 7 member 11 (SLC7A11) and SLC3A2 proteins (UniProt Q9UPY5). Once internalized, cystine is reduced to cysteine, which serves as the rate-limiting substrate for the two-step synthesis of glutathione (GSH) catalyzed by glutamate-cysteine ligase (GCL) and glutathione synthetase (GSS) (Gout et al., 2001, PubMed 11502712). This system is a primary defense against ferroptosis, an iron-dependent form of lipid peroxidation-induced cell death (Dixon et al., 2012, PubMed 22579052). In many cancers, this system is upregulated to counteract high metabolic oxidative stress, making components like SLC7A11 and GCL attractive therapeutic targets. Pharmacological inhibitors such as sulfasalazine (targeting SLC7A11) and buthionine sulfoximine (targeting GCL) are used to deplete GSH and sensitize tumor cells to oxidative stress-inducing therapies (PubMed 11502712, PubMed 23913102).

Other names

System xC-xCTCystine/glutamate transporterCystine/glutamate antiporterPlasma cystine / cellular cysteine–glutathione synthesis systemSLC7A11-GSH axis

Inhibition of the SLC7A11 transporter or the GCL enzyme disrupts the supply of cysteine or its ligation into glutathione, leading to depletion of the cellular glutathione pool and induction of ferroptosis (PubMed 22579052, PubMed 31439724).