Methods of treating ischemia by modulating ischemic cell bioenergetics are described. For example, the methods include the administration of small molecule, polypeptide, and/or genetic agents that modulate oxidative metabolism and/or glycolytic metabolism in ischemic cells, such as ischemic muscle cells. In some embodiments, the agent is adapted to deliver Cox6a2 or PFKFB3 to the cell. Also described are related pharmaceutical compositions and kits for the treatment of ischemia and ischemic injury related to, for instance, such as peripheral arterial disease, stroke, myocardial infarction, and diabetes.
