Spatial Patterning of Mitochondrial Energy Production in Mouse Eggs.

Metabolism provides a continuous flux of energy that sustains living systems out of equilibrium and gives rise to biological form and function. The spatiotemporal variations in mitochondrial localization and metabolic activities pattern energy production within cells. While precisely regulating these patterns is crucial during embryogenesis, the underlying biophysical mechanisms driving these emergent patterns remain unknown.

Mammalian development begins with the fusion of a mature egg and sperm. Before fertilization, mature eggs exist in a non-equilibrium steady state, characterized by an assembled meiotic spindle—a cellular machine that pushes chromosomes apart during cell division—positioned at the cell cortex. The spindle's positioning plays a crucial role in organizing mitochondria within the egg. This arrangement creates regions of higher and lower mitochondrial activity, a spatial pattern whose disruption is associated with age-related infertility. Despite its importance, we currently lack a mechanistic understanding of how the spindle's positioning creates the pattern of varying mitochondrial activity throughout the egg. To address this knowledge gap, I combine quantitative microscopy with biochemical and mechanical perturbations, interpreting the data using the lens of quantitative biophysical theory.

My findings reveal that individual mitochondria within a single egg possess distinct protein compositions, leading to variations in metabolic activity. Live tracking of mitochondrial motion and intracellular fluid flow suggests that spindle-generated cytoplasmic flows transport mitochondria, moving those with higher energy-generating capacity (membrane potential) closer to the spindle, where they likely support local energy demands. With this quantitative data, I am developing a hydrodynamic theory of intracellular flows to computationally model this pattern formation.

This work aims to provide a quantitative theory of mitochondrial organization and its interplay with spindle function, advancing our understanding of subcellular energy fluxes in early mammalian development. More broadly, it seeks to offer a quantitative understanding of the spatiotemporal patterning of thermodynamics fluxes in cells and a predictive theory of mitochondrial self-organization.