Mitochondria and cardiac hypertrophy.

Abstract

• Normally, myocardial metabolism is almost exclusively aerobic. The substantial quantities of adenosine triphosphate (ATP) required for muscle contraction and the much smaller amounts necessary for the maintenance of functions such as ion transport, rhythmicity, and conduction and the synthesis of membrane and protein constituents of the myocardium are supplied almost exclusively by mitochondrial oxidation of fatty acid and carbohydrate substrates. Even under conditions of stress such as those that exist during severe exercise, when the cardiac ATP requirement may be increased considerably, the capacity of the mitochondria for oxidative phosphorylation appears to be adequate to meet the requirements. The high level of and the capacity for oxidative metabolism in the heart are reflected morphologically in the remarkable observation that mitochondria constitute more than 35% of the cardiac cell volume as measured by quantitative electron microscopic stereological procedures (1). Acute changes in energy requirements such as those that occur during strenuous exercise appear to be effectively met by increased mitochondrial synthesis of ATP, and the synthesis is finely adjusted to ATP requirements by the respiratory control mechanism. Increased utilization of ATP results in transient accumulation of adenosine diphosphate (ADP), which acts as a phosphate acceptor and stimulates the mitochondrial oxidative rate by decreasing the level of mitochondrial high-energy intermediates (2) or the proton-motive force across the inner mitochondrial membrane (3), according to the chemical or chemiosmotic theories of oxidative phosphorylation, respectively. Sustained levels of increased preload or afterload, however, activate another more slowly re