Mitochondrial network complexity emerges from fission/fusion dynamics

Abstract: Mitochondrial networks exhibit a variety of complex behaviors, including coordinated cell-wide oscillations of energy states as well as a phase transition (depolarization) in response to oxidative stress. Since functional and structural properties are often interwinded, here we characterize the structure of mitochondrial networks in mouse embryonic fibroblasts using network tools and percolation theory. Subsequently we perturbed the system either by promoting the fusion of mitochondrial segments or by inducing mitochondrial fission. Quantitative analysis of mitochondrial clusters revealed that the structural parameters of healthy mitochondria lay in between the extremes of highly fragmented and completely fusioned networks. We confirmed our results by contrasting our emprirical findings with the predictions of a recently described computational model of mitochondrial network emergence based on fission-fusion kinetics. Altogether these results not only offer an objective methodology to parametrize the complexity of this organelle but add weight to the idea that mitochondrial networks behave as critical systems and undergo structural phase transitions.