Extent of Mitochondrial Hexokinase II Dissociation During Ischemia Correlates With Mitochondrial Cytochrome c Release, Reactive Oxygen Species Production, and Infarct Size on Reperfusion

Abstract

We propose that loss of mtHK2 during ischemia destabilizes mitochondrial contact sites, which, when accompanied by degradation of Bcl-xL, induces OMM permeabilization and cytochrome c loss. This stimulates reactive oxygen species production and mitochondrial permeability transition pore opening on reperfusion, leading to infarction. Consequently, inhibition of mtHK2 loss during ischemia could be an important mechanism responsible for the cardioprotection mediated by IP and other pretreatments.