The cystine/glutamate antiporter: when too much of a good thing goes bad

Glutamate excitotoxicity represents a major cellular component of ischemic brain injury. In this issue of the JCI, Soria and colleagues reveal that the cystine/glutamate exchanger is an important source of excitotoxic glutamate in response to ischemia induced by oxygen and glucose deprivation. As the exchanger is a primary determinant of both extracellular glutamate and intracellular glutathione, the findings from this study not only provide important insight into the mechanisms of brain ischemia but also demonstrate the complexity of the yin and yang of glutamate homeostasis and cellular redox balance.