Ultrastructural analysis reveals mitochondrial placement independent of synapse placement in fine caliber C. elegans neurons

Abstract

SUMMARYNeurons rely on mitochondria for an efficient supply of ATP and other metabolites. However, while neurons are highly elongated, mitochondria are discrete and limited in number. Due to the slow rates of diffusion of long distances it follows that neurons would benefit from an ability to control the distribution of mitochondria to sites of high metabolic activity, such as synapses. It is assumed that neurons’ possess this capacity, but ultrastructural data over substantial portions of a neuron’s extent that would allow for tests of such hypotheses are scarce. Here, we mined theCaenorhabditis elegans’electron micrographs of John White and Sydney Brenner and found systematic differences in average mitochondrial size (ranging from 1.4 to 2.6 μm), volume density (3.8% to 7.1%) and diameter (0.19 to 0.25 μm) between neurons of different neurotransmitter type and function, but found no differences in mitochondrial morphometrics between axons and dendrites of the same neurons. Analyses of distance intervals found mitochondria to be distributed randomly with respect to both presynaptic and postsynaptic specializations. Presynaptic specializations were primarily localized to varicosities, but mitochondria were no more likely to be found in synaptic varicosities than non-synaptic varicosities. Consistently, mitochondrial volume density was no greater in varicosities with synapses. Therefore, beyond the capacity to disperse mitochondria throughout their length, at least inC. elegans, fine caliber neurons manifest little in the way of subcellular control of mitochondria.SIGNIFICANCEBrain function is unequivocally reliant on mitochondrial function for its energy needs, and the mechanisms that cells use to control these organelles is an active field of enquiry. WormImage, a decades old electron microscopy database in the public domain, contains information about the ultrastructural disposition of mitochondria within the nervous system over previously unexamined extents. In a largely remote format, a team of undergraduate students, coordinated by a graduate student, mined this database over the course of the pandemic. We found heterogeneity in mitochondrial size and density between, but not within, the fine caliber neurons ofC. elegans. While neurons are clearly able to disperse mitochondria throughout their extent, we found little evidence that that they “install” mitochondria at synapses.