Figure 1: Proposed mechanisms by which HDACi induce ROS. (a) Mitochondrial injury. HDACi induces expression of Bid protein. This proapoptotic molecule binds to and disrupts the mitochondrial membrane, which results in increased ROS levels and apoptosis. (b) Alterations in antioxidant levels. HDACi upregulate the expression of thioredoxin-binding protein-2 (TBP-2). TBP-2 binds to and inhibits the antioxidant thioredoxin (Trx). This inhibition results in an imbalance of oxidants and antioxidants leading to increased ROS levels, which promotes apoptosis.