Several inherited and acquired disorders of mitochondria lead to defects in cardiac function as reflected in exercise intolerance, arrhythmias and heart failure. Manifestations of mitochondrial dysfunction is reflected in the abnormal mitochondrial proliferation, structure and ultimately as cytochrome C-induced apoptosis. How these defects are associated with disordered cytosolic events including SR calcium release and transcription has suggested a cross talk of mitochondria and cytosolic events that drive cardiomyocytes dysfunction.