Mitochondria Structure and Function Matures During Mammalian Cardiac Development

Abstract

The adult heart requires a precise coupling between oxidative metabolism, excitation and contraction to provide sufficient energy for each heart beat. In contrast, the early embryo, due to the hypoxic environment in utero, generates energy mainly through anaerobic glycolysis. Although the heart is the first organ to become functional in the embryo, ensuring effective circulation and embryonic survival by the mid-embryonic period, little is known about mitochondria as the embryonic heart matures. To investigate the role of energetics and mitochondrial biogenesis during murine cardiac development, we examined mitochondrial structure and function in whole hearts and cultured myocytes harvested throughout the embryonic period. Primary culture of embryonic ventricular myocytes at embryonic day (E) 9.5 displayed less mitochondrial mass and mitochondria that were shorter in length and less organized, as they did not associate closely with the contractile apparatus and resided primarily around the nucleus and cell periphery. Compared to E9.5, E13.5 ventricular myocytes displayed greater mitochondrial mass, and mitochondria that were longer, branched, networked, and more closely associated with the contractile apparatus. Data from whole hearts using multiphoton and electron microscopy confirmed these findings. Functional measurements indicated that mitochondrial membrane potential was higher at E13.5 than at E9.5, suggesting higher mitochondrial activity at later stages of development. Taken together, these data suggest that mitochondrial biogenesis and function may be important in the differentiation of early cardiac myocytes and the maturation of the heart.