Characterizing Mitochondrial Maturation in the Heart
Cardiovascular disease is the leading cause of death around the world and is only projected to become more severe. Because of their ability to supplant the heart’s weak regenerative capabilities, stem cells and their derivatives have been investigated as a potential therapy. However, stem cell-derived cardiomyocytes are less mature than the cells they would be replacing in a clinical setting, causing many functional shortcomings such as unorganized and weak contraction. An in-depth study of how maturation normally occurs is necessary to identify targets to enhance it. As one of the best known aspects of cardiomyocyte maturation, the mitochondria, and their substrate preferences, dictate the amount of energy a cell has as well as modulating a cell’s contraction, differentiation, and survival. In addition to the cell itself, the mitochondria mature over time. However, to what extent mitochondrial maturation drives cardiomyocyte maturation has not been investigated. In this study, we use quantitative PCR, western blotting, siRNA knockdown, and mass spectrometry to describe these developmental changes in mice. We identify COX7A1 as a novel marker of mitochondrial maturation as well as detail key shifts in the mitochondrial proteome over time.