Figure 8. Schematic model depicting the role of IRBIT-Bcl2l10 interplay in physiological and stress conditions.

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.

DOI: http://dx.doi.org/10.7554/eLife.19896.012