Presynaptic Mitochondrial Volume and Packing Density Scale with Presynaptic Power Demand

The work of Justs et al. (2022) utilizes a very elegant approach and advanced methodologies to correlate the estimated power demand of six presynaptic axon terminals with their mitochondrial volume and density in the Drosophila larva. These results provide a very valuable addition to our previously published results (Cserep et al., 2018), which confirmed a clear correlation between presynaptic energetic demands and mitochondrial volume/ultrastructure in mouse and human presynaptic terminals. In our primary work, we examined 70 presynaptic boutons from multiple populations using electron microscopy, transmission electron tomography, and other approaches. First, we compared two GABAergic bouton populations belonging to two well-characterized interneuron types. Their well-known physiological properties clearly confirm their differential energetic demands. More importantly, we could also compare mitochondrial parameters of glutamatergic presynaptic boutons within one population and correlate these parameters with the estimated energetic demands of these boutons based on their ultrastructural features – which eventually determine their power supply needs. We could perform these measurements on mouse, and also on post-mortem human brain samples.

The statement of the Authors in the abstract: „...but the relationship between presynaptic power demands and the volume available to the bioenergetic machinery has never been quantified.” seems to be a bit exaggerated, as this was the exact correlation we have described previously. We have shown that not only mitochondrial volume, but also crista-membrane density is correlated with presynaptic energetic demand, in a cell type-independent manner. Since crista-membranes harbor respiratory chain and ATP-synthase proteins, mitochondrial volume multiplied by crista density represents exactly the „volume available to the bioenergetic machinery”. Besides the first description of a cell type-independent coupling between presynaptic mitochondrial volume/ultrastructure and synaptic strength – responsible for local demand matching – we also suggested the possible presence of activity dependent ultrastructural remodeling of presynaptic mitochondria.

Nevertheless, the Authors corroborate our findings, and provide a very important extension, estimating the power demands of presynaptic boutons based on physiological measurements, and correlating these parameters with ultrastructural features using an elegant correlated electron microscopic workflow.

Justs et al., Presynaptic Mitochondrial Volume and Packing Density Scale with Presynaptic Power Demand, The Journal of Neuroscience, February 9, 2022 • 42(6):954–967

Cserep et al., Mitochondrial Ultrastructure Is Coupled to Synaptic Performance at Axonal Release Sites, eNeuro, January/February 2018, 5(1) e0390-17.2018 1–15