A Phase-Based Approach to Description of the Morphology and Topological Modes of Mitochondrial Network Fragmentation

Abstract

Mitochondria form a dynamic network within the cell, the morphology of which is determined by the balance of fusion and fission processes and is widely used as a phenotypic indicator of cell state. However, qualitative classes and one-dimensional morphometric indices poorly discern the global organization of the network and can combine topologically different states under the general label of “fragmentation.” In this paper, the authors propose a phase-based approach to describing mitochondrial morphology in terms of steady-state states of a dynamic graph and map connectivity regimes in a minimalistic stochastic model of edge rearrangements under fixed contact geometry. Network states were analyzed in the space of complementary topological parameters, including the fraction of vertices in the largest connectivity component C = S₁/N, the number of components N_c, the average degree ⟨k⟩, and the cyclomatic number β₁. It is shown that the fragmentation phenotype is not a unique morphological state and is characterized by pronounced structural heterogeneity, detectable only in a multidimensional topological description. Scanning the pfus control parameter revealed a transitional region of connectivity reorganization, localized by the maxima of Var(C) and percolation susceptibility x, reflecting increased component structure fluctuations in the final system. The proposed framework provides a foundation for a more rigorous interpretation of morphological phenotypes as a state space and for further comparison of microscopic data with models of mitochondrial network dynamics.