Abstract

Mitochondria are dynamic and complex organelles that play a central role in all aspects of biology, including energy production, intermediary metabolism, and apoptosis. These broad cellular functions also place mitochondria as a central player in human health and disease. We have focused recently on deciphering the biochemical and cellular functions of conserved uncharacterized mitochondrial proteins. This has revealed new mechanisms for several critical aspects of mitochondrial function, including the Mitochondrial Pyruvate Carrier (MPC), which is required for efficient mitochondrial pyruvate uptake. By perturbing the metabolic program of cells, MPC manipulation profoundly affects cellular decisions related to stem cell homeostasis and proliferation. This observation suggests that metabolism is not a passive enabler of cell behaviors, but instead plays a decisive role. One of our current areas of focus, which will be discussed, is to determine the mechanisms whereby metabolism and metabolites affect behaviors via direct modulation of proteins involved in signaling, transcription and other regulatory mechanisms. As we discover these mechanisms, which we hypothesize to be extensive within biology, we will be enabled to impinge on such phenomena for therapeutic benefit in disease states.