Exploring Mitochondria in the Intact Ischemic Heart

In describing human nature, the Irish author and satirist Jonathan Swift noted that “vision is the art of seeing what is invisible to others.” In the biological sciences, “vision” is transformed into a “science” as progress in imaging technology enables the uncovering of previously “invisible” intracellular programs. This capacity to “see inside cells” is improving in lock-step with advancing technologies that enable fluorophore-labeling of genes, proteins, cells, substrates, and metabolites. Thus, biomedical imaging is expanding our understanding of cellular function and disease pathophysiology. In this issue of Circulation , the practical application of 2-photon scanning laser microscopy is used to directly assess the mitochondrial inner membrane potential in the intact rat heart in response to cardiac ischemia and reperfusion.1Article p 1497 Before discussing this study, I will digress for a moment to review the relevance of mitochondrial function and the proposed role of the inner mitochondrial membrane potential on cardiac function and in its response to ischemia and reperfusion. The mitochondrion is central to cardiac function, as it modulates cardiac energetics, reactive radical biology, calcium homeostasis, and apoptosis.2 The inner mitochondrial membrane potential in turn reflects a composite of mitochondrial functioning, which means the maintenance of this electrochemical potential requires: (1) the functional integrity of electron transfer redox centers of oxidative phosphorylation; (2) the catalytic integrity of enzymes of β-oxidation and the Kreb’s cycle; and (3) the appropriate functioning of transport mechanisms linking the cytosol and the mitochondrial matrix.The mitochondrial inner membrane potential is not static; rather, the modulation of this electrochemical gradient directly controls mitochondrial adenosine triphosphate generation, Ca2+ flux, and the production and control of reactive oxygen species (ROS).3 Interestingly, modest modulation of the mitochondrial membrane potential appears to confer cellular adaptations that enhance …