Figure 5. Working model of the MICU1–MICU2 heterodimer and the regulation of Ca²⁺ uptake.

• A, B
  Space filling and cartoon representation of heterodimer structures in the Ca²⁺‐free (A) and Ca²⁺‐bound states (B). Both structures are built based on the MICU1 homodimer structure (PDB code: 4NSC) in the apo state. Ca²⁺‐free and Ca²⁺‐bound MICU1 were colored in wheat and gray, respectively. Ca²⁺‐free and Ca²⁺‐bound MICU2 were colored in purple and yellow, respectively. Calcium ions are shown as blue and red spheres in MICU1 and MICU2, respectively.
• C
  Comparison of MICU1–MICU2 structures in the apo (wheat and purple) and Ca²⁺‐bound states (gray and yellow). The conformational differences are highlighted by boxes (black dotted lines). The black arrows show the direction of the conformational change from apo to Ca²⁺‐bound state.
• D, E
  Proposed model for mitochondrial Ca²⁺ uptake regulated by MICU1–MICU2. In the apo state, MICU1–MICU2 form a loose complex which inhibits the uniporter. Upon Ca²⁺ binding, the conformational changes of the EF‐hands promote a transition to a more compact state, which activates Ca²⁺ uptake.