Orphaned mitochondria in heart failure

This editorial refers to ‘Impaired mitochondrial network excitability in failing guinea-pig cardiomyocytes’ by K.Y. Goh et al. , pp. 79–89. The heart is a highly efficient engine that relies on perfect tuning of all processes that support excitation–contraction (EC) coupling to pump blood to the body's organs. Since this engine must adapt its pumping capacity to any evolving variations in the metabolic demand of the organism, it possesses efficient control mechanisms on the cellular level to match ATP supply to the constantly varying cellular demand.1 In the heart, ATP is produced primarily in mitochondria, and the ATP pool is turned over in less than a minute. Due to this high energetic demand, 30% of the cellular volume is partitioned to mitochondria, which are aligned in a highly organized fashion in areas with the highest energetic demand, i.e. underneath the plasma membrane with its ATP-consuming ion transporters, and along the myofilaments, where myosin ATPase is the dominant consumer of cellular ATP.Two major factors that control mitochondrial respiration during workload transitions are Ca2+ and ADP. While ADP accelerates respiration and oxidizes the redox state of the energetic precursor NADH, Ca2+ activates the Krebs cycle to regenerate oxidized NAD+ to NADH.1 The close spatial alignment of mitochondria along the myofilaments and the sarcoplasmic reticulum (SR), the major cellular Ca2+ store, constitutes so-called microdomains in which privileged transfer of ADP and Ca2+ between myofilaments, the SR, and mitochondria is facilitated.1–3An important role for the spatial organization of mitochondria in this three-dimensional lattice within cardiac …