Mitochondrial Biogenesis and Maturation

The human heart consumes kilogram quantities of ATP daily to support persistent pump function. The vast majority of this ATP (>95%) is produced by mitochondrial oxidative phosphorylation (OXPHOS). Mitochondrial fatty acid oxidation (FAO) accounts for ≈60% to 90% of ATP production, whereas catabolism of carbohydrates contributes the remaining 10% to 40%. To support this high demand for ATP production, the developing cardiac myocyte has developed a tremendous capacity for mitochondrial biogenesis to establish this specialized mitochondrial system. Indeed, ≈40% of the cytoplasmic space within the adult cardiac myocyte is occupied by mitochondria. Importantly, the heart must continually adapt to changes in energy substrate availability, workload, and energy demands. Therefore, a complex regulatory network has evolved to dynamically match mitochondrial functional capacity with the energy demands of the heart during development and in diverse physiological contexts. Moreover, with pathological cardiac growth and remodeling, the heart also undergoes both contractile and energy metabolic reprogramming; fuel substrate preferences shift and the capacity and efficiency of mitochondrial ATP production is diminished. In this review, we describe the regulatory Review