Targeting mitochondria to protect the heart: a matter of balance?

Mitochondria are dynamic, undergoing both fission and fusion. Evidence indicates that a balance between these two processes is necessary to maintain a healthy state. With ischemia/reperfusion (I/R) of the heart, fission is enhanced and is associated with mitochondrial swelling, depolarization, and production of reactive oxygen species, as well as apoptosis. Accumulating evidence indicates that blocking fission is effective in reducing I/R-induced tissue damage and contractile dysfunction. In theory, enhancing fusion should also serve to prevent I/R-related heart damage. In this perspective article, we present evidence from preclinical studies over the last several years supporting the conclusion that targeting mitochondrial dynamics is a promising pharmacological strategy to protect the heart. Such an approach has great value in limiting heart damage from not only myocardial infarction but also medical interventional reperfusion, alcohol consumption, chemotherapy, and sepsis.