FIGURE 2 – New mechanisms involving mitochondrial Ca²⁺.

(A) CLIPT – Complex I interacts with MCU and maintains its protein turnover rate. (Adapted from ref. (68))

(B) Complex IV subunit COX7RP is estrogen dependent, sits at the interface between Complex III and IV, and promotes supercomplex assembly and respiratory efficiency. Increasing COX7RP led to reduced mitochondrial Ca²⁺ and ROS, whereas inhibiting its expression produced the opposite effects (see ref. (86)).

(C) Deactivated complex I promotes matrix acidification which dissolve CaP precipitates. The increased matrix Ca²⁺ triggers NCLX to exchange Ca²⁺ for Na⁺. Increased matrix Na⁺ decreases IMM fluidity and prevents CoQ diffusion, decreasing oxphos at Complex II + III. (Adapted from ref. (103))

(D) MCU binds to the subunit c of ATP Synthase in Trypanosoma (see ref. (92)). Excess Ca²⁺ may trigger rearrangement of the F₁ component of the ATP synthase to produce channels in the membrane component (see ref. (108)).