The mitochondrial permeability transition pore confers excitability and CICR wave propagation

Mitochondria have long been known to sequester cytosolic Ca and even to shape intracellular patterns of endoplasmic reticulum -based Ca signaling. Accumulating evidence suggests that the mitochondrial network is an excitable medium which can demonstrate Ca induced Ca release via the mitochondrial permeability transition. The role of this excitability remains unclear, but mitochondrial Ca handling appears to be a crucial element in diverse diseases as diabetes, neurodegeneration and cardiac dysfunction. In this report, we extend the modular Magnus-Keizer computational model for respiration-driven Ca handling to include a transition pore and we demonstrate both excitability and Ca wave propagation that is accompanied by depolarizations similar to those reported in cell preparations. These waves depend on the energy state of the mitochondria, as well as other elements of mitochondrial physiology. Our results support the concept that mitochondria can transmit state dependent signals about their function in a spatially extended way.