Sarcoplasmic reticulum and mitochondria in cardiac pathophysiology

Muscle cells, and in particular cardiomyocytes, consume a large amount of chemical energy to produce mechanical work. Myofilament contraction is regulated and synchronized within the cell by rapid, transient changes in the cytosolic Ca2+ concentration. Most of this calcium is released from the sarcoplasmic reticulum (SR), which has a large surface for Ca2+ transport, in close contact with the myofilaments. In between the myofilaments, cardiomyocytes are packed with mitochondria. These generate the energy needed for myofilament contraction, but serve also as an additional store for Ca2+. Thus, SR and mitochondria interact physiologically to control cellular Ca2+ homeostasis. It is partly through the Ca2+ loading of the mitochondria that their energy production is matched with the contractile energy demand. Mitochondria are now recognized as an essential effector structure determining cell death and survival. This is not only because of their central role in cellular energy metabolism, but also as key players in survival and death signalling. Alterations in the function of the SR are now known to be of primary importance for the development of hypertrophy and heart failure and in the genesis of life-threatening arrhythmias. Therefore, interaction between SR and mitochondria not only determines cardiomyocyte function under physiological conditions, but also is relevant for the development of cardiomyocyte dysfunction or death under pathophysiological conditions. The present Spotlight Issue of Cardiovascular Research aims to update our understanding of these important and rapidly evolving aspects of cardiac physiology and pathophysiology through a series of invited reviews and original contributions.