Figure 3. ATP production, Ca²⁺ movement, and mitochondrial dynamics in the inner (IMM) and outer mitochondrial membranes (OMM) in ventricular myocytes.

A. Top, confocal image of a ventricular cardiomyocyte showing the fluorescence of TMRM in mitochondria. Bottom, zoomed-in view showing a small region of the cell with 4–6 mitochondria. B. Schematic diagram of one of the intermyofibrillar mitochondria. The electron transport chain (ECT) is composed of five complexes: CI CII, CIII, CIV and CV. CI-CIV extrude protons to hyperpolarize IMM to approximately −160 mV. CV (the ATP synthase), uses the energy in ΔΨ_M to phosphorylate ADP to produce ATP. The adenine nucleotide translocase (ANT) exchanges ADP for ATP across the IMM. The voltage dependent anion channel is permeant to ATP, ADP, Ca²⁺, etc. The uncoupling proteins (UCPs) on the IMM regulates proton movement from the intermembrane space to the matrix in the production of heat. C. Mitochondrial Ca²⁺ entry and exit. MCU responsible for Ca²⁺ entry across the IMM is composed of the MCU, EMRE and MICUR1 subunits and is probably associated with one or more MICU1 (or MICU2 or MICU3) proteins. Ca²⁺ is extruded from the matrix by the Na⁺ dependent Ca²⁺ transporter, NCLX (also called the mitochondrial NCX, Na⁺-Ca²⁺ exchanger). D. Proteins involved with mitochondrial dynamics and quality control: OMM: Drp1 which associates with Fis1, Miff, MiD49/51; Parkin and PINK1; translocase of the OMM (Tom) complex, Mfn1, Mfn2. IMM: Opa1, translocase of the IMM (Tim) complex. Note: Tom and Tim proteins form a mitochondrial protein import path.