Figure 7.
Schematic Representation of the Proposed Model
In resting conditions (upper left), MICU1-MICU2 heterodimers act as the MCU gatekeeper, thanks to the prevailing inhibitory effect of MICU2; increases in calcium concentration (upper right) induce a conformational change in the whole dimer that releases MICU2-dependent inhibition and triggers MICU1-mediated enhancement of MCU channeling activity. Moreover, the removal of MICU1 with the consequent disappearance of MICU2 (lower left) leads to the loss of both gatekeeping at resting and cooperativity triggered by activation of calcium signaling. On the other hand, the selective removal of MICU2 (lower right) causes the loss of the gatekeeping mechanism but induces the formation of the MICU1-MICU1 homodimer that enhances mitochondrial calcium uptake after cellular stimulation. IMM, inner mitochondrial membrane.