Mitochondrial Morphologies Driven by Energy-Consuming Cell Sites in a Spatially and Time-Resolved Quality Model.

Abstract

Mitochondria are the energy plants of eukaryotic cells. Mitochondrial network morphologies are essential for the energy supply of eukaryotic cells. However, the associated dynamics are not yet fully understood. They behave as a dynamic network that adapts to the cell's environment and its energetic needs. Various processes such as mitochondrial fission and fusion, mitochondrial recycling, repair mechanisms, and oxidative stress influence the state of the mitochondrial network. Here, we introduce a novel time-dependent and spatially resolved quality model on mitochondrial morphology. The interplay between the mitochondrial network and energy-consuming cell sites is modeled by biophysical interactions of quality-dependent mitochondrial clusters in the presence of adenosine triphosphate (ATP) consumers represented by Mie potentials. Mitochondria are modeled as simplified ballistic particles that move within the cytoplasm of a virtual cell, and connect and divide by inelastic collisions. With this model, we investigate the coupling of mitochondrial dynamics with oscillating cell functions, representing diverse global states of the energetic architecture in the cell. Our simulations based on a generalized cell reveal a perinuclear condensation of mitochondria during phases of high-energy demand. Furthermore, quality-increasing mechanisms disclose the benefits of high mitochondrial masses. Simulations reveal that varying energy demands modeled by oscillations of ATP consumers alter the morphology of the network. Phases of high-energy consumption lead to interconnected network structures and perinuclear condensation of mitochondria. The model explains quality-increasing benefits of high mitochondrial masses.