Trx1 in cytoplasm, Trx2 in mitochondria forms a complex with ASK1 in resting cells to retain ASK1 in an inactive state. Proapoplotic stimuli (such as TNF and ROS) dissociate Trx1 and Trx2 from ASK1 leading to ASK1 activation. ASK1 in cytoplasm mediates a JNK-dependent apoptotic pathway assosiated with JNK activation, Bid cleavage, and Bax translocation. ASK1 in mitochondria mediates a JNK-independent apoplotic pathway. The two pathways appear to converge at cytochrome c release and caspase-3 activation. Thus, Trx1 and Trx2 cooperatively inhibit ASK1-mediated apoptosis.