Size Matters!

Structure dictates function. We have learned first-hand how this is true throughout our education. For example, we know that if alanine is substituted for a lysine in the active site of an enzyme, that protein will no longer serve its proper function. Haven’t covered that part of biochem review yet (uh oh)? Here’s another example then: it’s going to take you a lot longer to finish your soup with a knife instead of a spoon, right? (No, sipping from the bowl doesn’t count). This statement proved true yet again in a recent study showing that the size of axonal mitochondria is essential in neuronal calcium regulation. In this study, Lewis and colleagues studied axonal mitochondria in pyramidal neurons. Compared to the long and tubular mitochondria of the dendrites, mitochondria in the axon are shorter and spherical. However, the reason behind the differing shape and size between these mitochondria was unknown until recently. Research has studied dendritic mitochondria mainly in the context of neurodegenerative diseases while axonal mitochondria is known to be involved in axonal branching, ATP production (duh, powerhouse!), and calcium buffering. Yet, according to the researchers, no one had investigated the effects of what happens if you manipulate axonal mitochondrial size. So that’s what they did. Researchers downregulated Mitochondrial fission factor (MFF), a gene that controls mitochondrial fission (division). When MFF was turned off in mice, axonal mitochondria significantly increased in size and calcium intake. Increased calcium uptake resulted in decreased neurotransmitter release (remember our dear SNARE hypothesis) and subsequently decreased neuronal activity between neurons. Additionally, this change resulted in decreased axonal branching. Interestingly, the change in size did not change mitochondria’s ability to act as powerhouses, they can do that in their sleep I guess. Ultimately, the investigators showed that mitochondrial size matters and I’m sure they will soon discover even more dynamic mechanisms that these little guys are capable of.

Lewis, T. L., Kwon, S.-K., Lee, A., Shaw, R., & Polleux, F. (2018). MFF-dependent mitochondrial fission regulates presynaptic release and axon branching by limiting axonal mitochondria size. BioRxiv, 276691. https://doi.org/10.1101/276691