During cardiac ischemia-reperfusion in rats, the expression of Epac1 in the heart was upregulated, activating the downstream protein Rap1 to initiate a signal transduction cascade that resulted in the inhibition of mitochondrial fusion, promotion of mitochondrial fission, disruption of mitochondrial homeostasis and function, and activation of mitochondrial pathway-mediated cardiomyocyte apoptosis. The gene discussed is RAPGEF3; the disease is ischemia.