Dissecting subcellular metabolic gradients in mouse oocytes

• Applicant: Dr. Xingbo Yang, Ph.D.
• Subject Area: Biophysics ; Biochemistry ; Developmental Biology ; Cell Biology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 568548983

Cell metabolism provides energy and building blocks to sustain life activities. Metabolic activities need to be regulated and adapted to meet the energy and biosynthesis demand during organism development. Due to limitations in the technology to measure metabolic activities in living cells with sufficient spatiotemporal resolution, our understanding of the spatiotemporal control of metabolism in development is significantly lacking. Our lab has developed the first quantitative technique to measure metabolic fluxes through mitochondrial electron transport chain (ETC flux) with subcellular resolution in living cells. Using this technique, we have discovered subcellular metabolic gradients of ETC flux within a single mouse oocyte, where the ETC flux is higher in mitochondria closer to the cell membrane and lower in mitochondria closer to the meiotic spindle. The observation has revealed, for the first time, the existence of heterogeneities in mitochondrial metabolic flux within a single cell. This project aims to dissect the mechanism underlying the formation of the ETC flux gradient in mouse oocytes and to explore the biological functions of the metabolic gradient. We hypothesize that the ETC flux gradient is either due to reaction-diffusion of signalling molecules or due to metabolism-driven self-sorting of mitochondria. We expect our research to lead to the discovery of relevant signalling molecules or new mitochondrial self-organization mechanisms that contribute to the formation of subcellular metabolic gradients.

• DFG Programme: Research Grants