This project evaluates fundamental but largely unexplored mechanisms as to how cells maintain the integrity of one of their most critical internal compartments, their energy factories termed mitochondria. To maintain proper mitochondrial function, it is thought that damaged or dysfunctional mitochondria are routinely removed and replaced with new ones, but how cells coordinate this process is poorly understood. The project is designed to determine how different mitochondrial subpopulations within cells, distinguished from one another based on differences in size, energy-producing activity, and other endpoints, are either amplified or removed in response to specific cues that work in concert to coordinate cellular function. This research incorporates many important teaching and training goals by engaging students across academic levels (including high school, undergraduate, and graduate students) and backgrounds through their participation in research activities involving the application of next-generation scientific tools to drive new discoveries. The project specifically encourages, and implements a recruiting strategy for, the active participation of under-represented high school and undergraduate students interested in pursuing careers in STEM (Science Technology Engineering Mathematics).
How subpopulations of mitochondria are differentially governed to maintain homeostatic balance between mitochondrial integrity and dysfunction are not known. Although mitochondria are heterogeneous with respect to function, DNA content, and morphology, little is understood regarding how mitochondrial properties are regulated on a per organelle basis, and why some mitochondria have a function distinct from others in the same cell. A major unresolved question in cell biology revolves around how 'mitochondrial heterogeneity' arises, and how variability between mitochondrial subpopulations can impact cellular functions. This project will test the hypothesis that distinct populations of mitochondria are preferentially allocated and set aside by the cell, but can be triggered to activate under certain physiological conditions, while dysfunctional mitochondria are preferentially eliminated via mitophagy (selective degradation of mitochondria by the cell). This fundamental knowledge and insight into how mitochondrial subpopulations can be differentially governed extends the current understanding of intracellular organization and is broadly applicable across eukaryotes. It is anticipated that this research will drive novel discoveries in normal cells, and will lead to new mitochondrial-based therapeutic platforms and molecular interventions in pathophysiologic states.
