Figure 1. Ionic pathways across the mitochondrial inner membrane just before and after irradiation.

Pathways and components include the electron transport chain (complexes I-IV), ATP synthase (complex V), uncoupling proteins (UCP), mitochondrial Ca²⁺ uniporter (MCU), mitochondrial permeability transition pore (MPTP) and proton motive force (PMF, made up of membrane potential and the proton gradient). A. The moment just before ionizing radiation-induced ROS (radROS) and Ca²⁺ arrive at and cross the membranes (blue pathways), showing normal, coupled respiration at moderate levels of O₂ uptake and ATP synthesis, accompanied by moderate electron leak and mtROS. B. The moment just after radROS and Ca²⁺ (at physiological levels) stimulate transient depolarization, ATP synthesis and O₂ uptake, leading to electron emission from the electron transport chain, mtROS surge on both sides of membrane and UCP partial uncoupling (blue pathway). Overload Ca²⁺ influx and excessive mtROS cause Ca²⁺ to leave the mitochondrion via the MPTP and lead to apoptosis (blue dashed pathway).