Glycolysis and fatty acid β-oxidation, which one is the culprit of ischemic reperfusion injury?

Thrombolysis therapy and percutaneous coronary intervention are common methods in the treatment of acute myocardial infarction. These methods can recover the cardiac function in most cases. But in almost one-third circumstances, cardiac dysfunction and structural damage aggravated, which is known as ischemia-reperfusion injury. Normally, most ATP in cardiomyocytes was produced from fatty acid beta-oxidation. However, both fatty acid beta-oxidation and glycolysis accelerated due to AMPK activation during ischemic. Glycolysis uncoupled from oxidation results in intermediate metabolite accumulation, such as lactate, proton, succinate and NADH. During reperfusion, the recovering rate of fatty acid beta-oxidation even exceed the rate under physiological condition due to the sudden influx of high concentration of oxygen. High rate of fatty acid beta-oxidation inhibits glycose oxidation and results in proton and Ca2+ overload, especially huge amount of ROS production, which leads to mitochondria damage and cell death. Clearly, energy metabolism disorder result from the sudden change of oxygen supply during ischemic and reperfusion is the main cause of ischemic reperfusion injury. However, glycolysis and fatty acid beta-oxidation, which one is the real culprit in ischemic reperfusion injury is controversial. In this review, we will discuss the process of glucose metabolism and fatty acid beta-oxidation thoroughly, as well as the energy sensor AMPK signaling, in order to clarify how to modulate energy metabolism to reduce injury during ischemic and reperfusion.