We study the roles that mitochondria play in development, health, and disease. In addition to their established role in bioenergetics, mitochondria regulate many cell processes by contributing to the biosynthesis of nucleic acids, lipids, and proteins. They also control cell responses to stress by signaling via the release of reactive oxygen molecules to the cytosol. Mitochondria also participate in signaling through their uptake or release of ionized calcium. Mitochondria are involved in multiple functions related to signaling through their generation of metabolic substrates involved in protein (including histone) methylation and demethylation, as well as protein acetylation and deacetylation. We study these functions with particular interest in perinatal disorders associated with prematurity, as well as in cardiopulmonary diseases. Finally, we investigate how mitochondrial functions affect tumorigenesis and tumor phenotypes in cancer.
Paul T. Schumacker, MEng, PhD, ATSF, FERS
MITOCHONDRIAL FUNCTIONS REGULATE CARDIOMYOCYTE PROLIFERATION
This project examines the role of mitochondria in regulating cell proliferation in the heart. Newborn heart cells are capable of undergoing cell division, which can repair heart damage with new muscle cells during the perinatal period. However, soon after birth, these cells transition from fetal myocytes into adult heart cells that have lost the ability to divide. After this transition has occurred, damaged hearts are repaired with scar tissue, which interferes with normal contraction and can contribute to heart failure. We have discovered that mitochondria regulate the heart cell's transition from mitosis-competent into a post-mitotic state. During that transition, the heart cells switch from a fetal reliance on glycolysis to the adult reliance on oxidative phosphorylation. Forcing the adult heart cells to return to a reliance on glycolysis causes a re-awakening of their ability to undergo cell division, and the hearts grow in size by turning on gene pathways associated with cardiac development. This response, when activated concurrently with the induction of ischemic injury, results in the migration of new heart cells into the region of cell damage, opening the possibility that this response could be used to repair under-developed left hearts in newborns, or to repair ischemic damage in adult hearts.