The normal process of acidification of the endocytic vesicle containing diphtheria toxin (DT A:B) associated with target cell proteins HBEGF and CD9 is thought to cause a conformational change in the toxin. Its B fragment forms a channel in the endocytic vesicle membrane through which the A fragment is extruded into the target cell cytosol. There, reduction of the disulfide bond connecting the A and B fragments releases the A fragment to refold. The process requires participation of target cell heat shock proteins (HSP90AA1 and HSP90AB1) and thioredoxin reductase 1 (TXNRD1), which may mediate disulfide bond cleavage (Ratts et al. 2003; Murphy 2011).