Figure 2.

The m-AAA protease regulates MCU complex assembly by mediating the degradation of non-assembled EMRE subunits. An EMRE-MICU assembly intermediate binds to MCU subunits to form a gated MCU complex, while the m-AAA protease degrades non-assembled EMRE subunits. In the absence of the m-AAA protease, excess EMRE can bind either to MICU to form gated MCU complexes or can interact directly with MCU resulting in the formation of constitutively open MCU complexes lacking MICU regulatory proteins. This increases the vulnerability of cells to Ca²⁺ overload and Ca²⁺-induced cell death.