The function of mitochondrial networks

Mitochondria are dynamic energy-producing organelles, and there can be hundreds or even thousands of them in one cell. Mitochondria (as we've blogged about before - e.g. here) do not exist independently of each other: sometimes they form giant fused networks across the cell, sometimes they are fragmented, and sometimes they take on intermediate shapes. Which state is preferred (fragmented, fused or in between) seems to depend on, for example, cell-division stage, age, nutrient availability and stress levels. But what is exactly the reason for the cell preferring one morphology over another?

Nonlinear phenomena -- like some percolation effects -- could help account for the functional advantage of mitochondrial networks

We recently wrote an open-access paper (free here in the journal BioEssays) in which we try to answer the question: what is it about fused mitochondrial networks that could make them preferable to fragmented mitochondria? Our paper differs from previous work in that we attempt to use a range of mathematical tools to gain insight into this complex biological system and we try to hit on the root physiological and physical roles. We use physical models, simulations, and numerical estimations to compare ideas, to reason about existing hypotheses, and to propose some new ones. Among the possibilities we consider are the effects of fusion on mitochondrial quality control, on the spread of important protein machinery throughout the cell, on the chemistry of important ions, and on the production and distribution of energy through the cell. The models we use are quite simple, but we propose ideas for improving them, and experiments that will lead to further progress.

Taking a mathematical perspective leads to a central idea: for fused mitochondria to be 'preferred' by the cell, there must be some nonlinear advantage to fusion. That's what the fuzzy line is representing in the figure above. A big mitochondrion formed by fusing two smaller ones must in some sense be 'better' than the sum of the two smaller ones, or there would be no reason why a fused state is preferred.

Mitochondria can fuse to form large continuous networks across the cell. From a mathematical and physical viewpoint, we evaluate existing and novel possible functions of mitochondrial fusion, and we suggest both experiments and modelling approaches to test hypotheses

What is the source of this nonlinearity? We find several physical and chemical possibilities. Large pieces of fused mitochondria are better at sharing their contents (e.g. proteins, enzymes, and possibly even DNA) than smaller pieces of fused mitochondria. If the 'fusedness' of the mitochondrial population increases by a factor of two, the efficiency with which they share their contents increases by more than two! Also, fusion can reduce damage. If a mitochondrion gets physically or chemically damaged, having some fused non-damaged neighbours can help to reduce the overall harm to the cell. Finally, fusion may increase energy production because of a nonlinear chemical dependence of energy production on mitochondrial membrane potential. Fusing more mitochondria may, under certain circumstances, have the effect of increasing energy production. Hanne, Iain and Nick

Flow with the Grow

In order to remain metabolically active, living things require a source of energy, and a regular supply of molecules of various kinds. As living things are composed of cells, large organisms inevitably face a fundamental challenge: they need to supply all of their component cells with the resources needed for survival. Mammals have cardio-vascular systems, plants have xylem and phloem, but how do fungi tackle the fundamental transport challenge? Compared to the other major kingdoms of multi cellular life, transport in fungi is poorly understood. This is somewhat surprising, as transport in fungi is an ecologically critical process. Fungi are an essential component of soil: without fungi leaf litter would not degrade, and many fungi form foraging networks which circulate carbon, nitrogen and phosphate. If a fungus grows, that increase in volume must come from somewhere: if the source of new volume is distant from the growth then this must create flows in the network. Because the volume is mostly water, which here is effectively incompressible, growth in one part of the network will be rapidly coupled to the rest. We suggest that fluid flows associated with growth might themselves be the major form of long-range transport in fungi. To investigate transport in fungi and the developmental logic of fungal networks, we photographed growing fungal networks, and digitized the images to produce a sequence of matrices that describe how the networks change over time. For each sequence of networks we identify a set of fluid flows which are as small as possible whilst being consistent with the observed changes in volume. We found that those parts of the network that were predicted to carry a large current typically thickened over time, while other parts of the network became thinner, or were consumed by the fungi in order to fuel further exploratory growth. So our crude idea (that flows are directly coupled to growths) did seem to be, at least partly, consistent with the data. You'll find our paper "Growth-induced mass flows in fungal networks" here and in its journal version (free, from Nov 2011, at the Proceedings of the Royal Society B) here. The Institute for Science, Innovation and Society did a blog on this article as well. Luke and Nick