 Emergence of the Mitochondrial Reticulum from Fission and Fusion DynamicsValerii M Sukhorukov, Daniel Dikov, Andreas S Reichert and Michael Meyer-Hermann PLOS Computational Biology, 2012, vol. 8, issue 10, 1-13 Abstract: Mitochondria form a dynamic tubular reticulum within eukaryotic cells. Currently, quantitative understanding of its morphological characteristics is largely absent, despite major progress in deciphering the molecular fission and fusion machineries shaping its structure. Here we address the principles of formation and the large-scale organization of the cell-wide network of mitochondria. On the basis of experimentally determined structural features we establish the tip-to-tip and tip-to-side fission and fusion events as dominant reactions in the motility of this organelle. Subsequently, we introduce a graph-based model of the chondriome able to encompass its inherent variability in a single framework. Using both mean-field deterministic and explicit stochastic mathematical methods we establish a relationship between the chondriome structural network characteristics and underlying kinetic rate parameters. The computational analysis indicates that mitochondrial networks exhibit a percolation threshold. Intrinsic morphological instability of the mitochondrial reticulum resulting from its vicinity to the percolation transition is proposed as a novel mechanism that can be utilized by cells for optimizing their functional competence via dynamic remodeling of the chondriome. The detailed size distribution of the network components predicted by the dynamic graph representation introduces a relationship between chondriome characteristics and cell function. It forms a basis for understanding the architecture of mitochondria as a cell-wide but inhomogeneous organelle. Analysis of the reticulum adaptive configuration offers a direct clarification for its impact on numerous physiological processes strongly dependent on mitochondrial dynamics and organization, such as efficiency of cellular metabolism, tissue differentiation and aging. Author Summary: Mitochondria control energy production, initiation of cell death and several other critical cellular processes. Most often, they form a constantly reshaping tubular reticulum spread over the cytosol. Despite extensive knowledge of mitochondrial physiology, accurate description of their large-scale architecture is missing, partly due to substantial variability of reticulum geometries found in different cell types, and a capability for fast radical changes. We address this shortcoming with a mathematical model representing the organelle as a cell-wide dynamical network subjected to opposing actions of fission and internal fusion – processes known experimentally but not yet accurately specified. This opens a way for the quantitative characterization of the large-scale organization by showing how particular types of the internal dynamics can shape the reticulum into the whole multitude of configurations observed in biological studies. Further analysis reveals that for a specific value of tip-to-side fission/fusion rates the network should undergo a radical reorganization. Because of the high morphological sensitivity to minute changes in fusion or fission rates close to the critical point, cells can quickly adapt the mitochondrial operation and structure to their actual needs at a low expenditure of energy. Date: 2012 Downloads: (external link) Related works: Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text Persistent link: https://EconPapers.repec.org/RePEc:plo:pcbi00:1002745 DOI: 10.1371/journal.pcbi.1002745 Access Statistics for this article More articles in PLOS Computational Biology from Public Library of Science |
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