In physiological conditions, in WT cells, IRBIT promotes ER-mitochondria contact rendering Ca2+ transfer easier between the two organelles. The additive effect of Bcl2l10 and phosphorylated IRBIT on IP3R maintains Ca2+ transfer at a low level. In IRBIT KO cells, the amount of Ca2+that is released through IP3R is increased due to absence of IRBIT, but Ca2+ transfer to the mitochondria is reduced because of the great reduction of ER-mitochondria contact. Following an apoptotic stimuli, Ca2+ release from the ER is increased. In WT cells, IRBIT dephosphorylation induces its translocation into the cytosol together with Bcl2l10, allowing a massive Ca2+ transfer from ER to mitochondria. By contrast, in IRBIT KO cells, Bcl2l10 is no longer displaced from MAMs, reducing the release of Ca2+from ER. This, combined with the reduction of ER-mitochondria contact, prevents massive Ca2+ transfer to mitochondria and thus greatly attenuates apoptosis.