Figure 3. The ATP synthasome and its interacting partners.

A,B. The term ‘ATP synthasome’ refers to the supramolecular complex composed of the F₁F_O-ATP synthase, ANT and PIC. The F₁F_O-ATP synthase harnesses the electrochemical gradient generated by the respiratory chain across the inner mitochondrial membrane (IMM) to catalyze the synthesis of ATP, whereas PIC and ANT ensure the availability of inorganic phosphate and ADP, respectively. The ATP synthasome interacts with CYPD, a protein of the mitochondrial matrix, and the VDAC1-HKII complex, which is assembled at the outer mitochondrial membrane (OMM). On one hand, these interactions allow ATP molecules produced by the F₁F_O-ATP synthase to be channeled to the mitochondrial surface and support the HKII-mediated conversion of glucose into glucose-6-phosphate (G6P). On the other hand, they place the ATP synthasome in a privileged position to contribute to (or regulate) the so-called ‘permeability transition pore complex’ (PTPC), the supramolecular entity that mediates the mitochondrial permeability transition (MPT). CK, creatine kinase (official name: creatine kinase, mitochondrial 1, ubiquitous) IMS, intermembrane space. Molecular graphics and analyses were performed with the UCSF Chimera package. Chimera is developed by the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco (supported by NIGMS P41-GM103311).