Failed Power Plant Turns Into Mass Murder
New Insight on Mitochondrial Cardiomyopathy
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Mitochondria are known as the powerhouse of the cell. For a high-energy–consuming organ, such as the heart, continuous ATP production via oxidative metabolism in the mitochondria is essential. Apart from ATP generation, mitochondria are also key to the regulation of cellular metabolism, calcium homeostasis, and reactive oxygen species (ROS) generation.1 Mitochondrial dysfunction has been strongly implicated in a variety of cardiovascular diseases including ischemic heart disease and heart failure. Furthermore, a large portion of mitochondrial disease patients, a condition caused by mutation of genes for mitochondrial proteins, develop cardiomyopathy indicating a causal role of mitochondria in cardiac dysfunction. Given its significant role in the pathogenesis and the current lack of effective therapy for mitochondrial dysfunction, there is a clear need for discovery and innovation in mitochondrial medicine.2,3
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It is well established that the fetal heart relies heavily on glycolysis for energy metabolism. A switch from glycolysis to oxidative metabolism in the early postnatal period is associated with explosive mitochondrial biogenesis.4,5 The switch is critical for the postnatal maturation of the heart. Loss of PGC-1α/β (peroxisome proliferator–activated receptor gamma coactivator), the powerful transcriptional regulators of mitochondrial biogenesis, in perinatal and postnatal periods, results in lethal cardiomyopathy.6,7 The role of mitochondria in the embryonic cardiomyocytes is, however, less explored. Recent studies using pluripotent cell–derived cardiomyocytes have suggested intriguing functions of mitochondria beyond energy provision in the regulation of cardiomyocytes maturation.6,8–10 …