Dimerization of Smac is crucial for its mitochondrial retention by XIAP subsequent to mitochondrial outer membrane permeabilization

► We identified that physiological expression of XIAP selectively prolongs the release of dimeric Smac but not monomeric Smac. ► Dimeric Smac cannot efficiently leave the mitochondria if elevated amounts of XIAP are present. The release of monomeric Smac instead is not affected. ► In contrast to Smac dimerization, the dimerization of XIAP via its BIR1 region does not influence the kinetic or the efficiency of Smac release.