ABSTRACT
Mitochondrial dysfunction is well documented in experimental models of cardiac aging, ischemia reperfusion injury, hypertensive cardiomyopathy and heart failure. The dysfunction includes increased mitochondrial oxidative stress, mitochondrial DNA depletion and increased mitochondrial DNA mutation or deletion frequency, impaired mitochondrial respiration due to dysfunction or decreased protein levels of respiratory complexes, impaired mitochondrial autophagy and dynamics as well as pertubation of mitochondrial calcium homeostasis. In this chapter we will discuss all of the above changes leading to mitochondrial dysfunction in the context of cardiac aging, hypertensive cardiomyopathy, ischemia reperfusion, experimental heart failure and cardiac arrhythmia. We will focus specifically on mitochondrial oxidative stress and how the reactive oxygen species (ROS) signaling interact with calcium homeostasis, mitochondrial DNA, autophagy and dynamics as well as NAD+-dependent sirtuin signaling. The mechanisms of mitochondrial signaling in the regulation of ion channel function will be discussed.
