Abstract 2284 Using Molecular Dynamics to Determine the Mechanism of Chloride Dependence in System xC-

The human transmembrane protein system xC-, an antiporter of glutamate and cystine, has been targeted in the treatment of cancer and a wide array of neurodegenerative disorders due to its roles in combating ferroptosis and oxidative stress. Analysis of system xC- activity in cultured human glioma cells has shown cystine uptake to be dependent on extracellular chloride concentration. The long-term objective of this study is to understand the mechanism by which chloride ions enable cystine uptake by system xC-.