A Role for Peroxisome Proliferator-Activated Receptor γ Coactivator-1 in the Control of Mitochondrial Dynamics During Postnatal Cardiac Growth

H igh energy demands of the postnatal heart are largely satisfied by ATP generated via mitochondrial oxidative phosphorylation (OXPHOS). Accordingly, cardiac myocytes require a specialized, high-capacity mitochondrial system. The importance of mitochondrial respiration for proper heart function is demonstrated by the tight linear relationship between cardiac oxygen consumption and work. 1 Evidence is emerging that in many forms of heart failure, cardiac mitochondria revert to prenatal levels of function and morphology, leading to energy starvation, contributing to a vicious pathological cycle. 2,3 During cardiac development, mitochondria undergo a matu-ration process. Mitochondrial maturation can be divided into 3 main developmental stages: prenatal, perinatal, and postnatal. In the prenatal stage, the early embryonic heart relies largely on nonmitochondrial energy sources (ie, anaerobic glycoly-sis). 4 During the transition from late fetal to postnatal periods (perinatal stage), the mitochondrial functional capacity of the heart increases dramatically, supporting a switch to reliance on fatty acids as the chief energy substrate. 4–6 This increase in mitochondrial oxidative capacity is triggered by a burst of Rationale: Increasing evidence has shown that proper control of mitochondrial dynamics (fusion and fission) is required for high-capacity ATP production in the heart. Transcriptional coactivators, peroxisome proliferator-activated receptor γ coactivator-1 (PGC-1) α and PGC-1β, have been shown to regulate mitochondrial biogenesis in the heart at the time of birth. The function of PGC-1 coactivators in the heart after birth has been incompletely understood.