UCLA

An imbalance in energy homeostasis leads to increased lipid storage and obesity. Mechanisms that regulate cellular lipid storage or utilization are thought to play a key role in maintaining energy balance and overall metabolic health. However the mechanisms that regulate energy expenditure and fuel utilization are not well understood. Here we address these gaps in knowledge by first describing a novel mechanism to increase energy expenditure by regulating mitochondrial fuel utilization. We find that blocking pyruvate entry into the mitochondria increases energy expenditure by activating an ATP-demanding lipid cycle of LD breakdown and buildup that is fueled by lipid oxidation. Moreover, recent studies have demonstrated heterogeneity in mitochondrial function, and identified a unique population of BAT mitochondria that support lipid storage by anchoring themselves to LD and facilitating TG synthesis and LD expansion. However, it remains unknown if these unique mitochondria are conserved in other tissues. Here, I describe the development of the first approach to isolate PDM from WAT. Using this approach I show that PDM in WAT have a unique function that is distinct from BAT. Future research understanding the mechanisms that control subpopulations of mitochondria and their roles in lipid homeostasis can provide novel methods of altering energy metabolism through mitochondria.