Spatial Patterning of Mitochondrial Energy Production in Mouse Oocytes

Metabolism provides a continuous flux of energy that keeps living systems out of equilibrium and gives rise to biological form and function. The organization of mitochondria and spatial distributions in mitochondrial activity determine the spatiotemporal pattern of energy production within cells, precise control of which is crucial to mammalian embryo development and fertility. Despite its central importance, we currently lack a mechanistic understanding of the physical processes that give rise to these emergent patterns in mammalian embryos.

In this talk, I will share my ongoing work on deciphering the mechanism behind the formation of subcellular spatial patterns of mitochondrial metabolism in metaphase II arrested mouse oocytes, the first stage of development. At this non-equilibrium steady state, there exists a spatial gradient of mitochondrial metabolism with distance from the meiotic spindle, but the causes and consequences of this gradient are unknown. To decipher the physical mechanism underlying the origin of this gradient, I am integrating quantitative microscopy with biochemical and mechanical perturbations, with the aim of interpreting the data using the lens of continuum biophysical theory.

My current experiment suggests that individual cells contain functionally distinct mitochondria, and their internal state governs their actin-dependent mobility. Finally, the spatial location of the meiotic spindle dictates the direction of mitochondrial motion, which, coupled with the observed metabolism-dependent mitochondrial motility, causes the self-organization of mitochondria to give rise to large-scale spatial patterning of energy production.

Understanding these mechanisms in mouse oocytes will lead to the development of a quantitative description of the spatiotemporal patterning of thermodynamics fluxes in cells and contribute to building a predictive theory of mitochondrial self-organization. It will also provide mechanistic insight into the critical role of sub-cellular energy fluxes in early mammalian development and reveal the physics of how energy fluxes influence the collective behavior of living active matter.