Every cell must constantly monitor its energy level and appropriately adjust energy production rates, based on metabolic demand to maintain homeostasis. Continuous fulfillment of this energy demand depends on sufficient nutrient supply, sensing nutrient availability, metabolizing and converting into chemical energy. In eukaryotic cells energy, in the form of ATP, is mainly produced by mitochondria. Not only how much total ATP is generated, local energy level is also important for cells to carry out critical functions, such as neuronal activity, cell migration, tumor cell invasion, wound healing, and immunity. Intracellular transport and positioning of mitochondria shape spatiotemporal heterogeneity in ATP distribution. My overall goal is to understand the molecular pathways regulating the interplay between cellular metabolism, mitochondrial positioning and function. The estimated mitochondrial protein number is ~1,200 for mammalian cells. Post- translational modifications can further magnify the functional diversity of proteins. Metabolic flux- sensitive post-translational modification, O-GlcNAcylation, uniquely couple nutrient status to cellular metabolism and signaling pathways. While my research will be focused on O- GlcNAcylation-dependent regulation of mitochondrial functions, systematic analysis of metabolic enzyme functions within the intracellular space will add extra dimension to our understanding of metabolic pathways. Our experiments will decipher the metabolic biochemistry and metabolite kinetics within the context of cellular architecture. My interdisciplinary research program is poised to reveal fundamental insights into the mechanisms that orchestrate the nutrient and energy supply, and pinpoint the underlying causes of energy impairments that lead to diseases. !
Cells allocate substantial resources towards monitoring their energy level, and appropriately adjust energy production rates based on the metabolic demand and nutrients status to maintain homeostasis. This proposal aims to understand how cellular metabolic state regulates mitochondrial function and dynamics, and how it contributes to bioenergetics in the cells. These studies will produce important insights into the biochemical pathways that underlie cell migration in cancer and wound healing, nervous system development, endocrine and metabolic diseases, nutritional and mitochondrial disorders, and obesity.
|Yu, Seungyoon B; Pekkurnaz, Gulcin (2018) Mechanisms Orchestrating Mitochondrial Dynamics for Energy Homeostasis. J Mol Biol 430:3922-3941|