Morphological principles of neuronal mitochondria

In the highly dynamic metabolic landscape of a neuron, mitochondrial membrane architectures can provide critical insight into the unique energy balance of the cell. Current theoretical calculations of functional outputs like adenosine triphosphate and heat often represent mitochondria as idealized g...

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Bibliographic Details
Published in:Journal of comparative neurology (1911) Vol. 530; no. 6; pp. 886 - 902
Main Authors: Mendelsohn, Rachel, Garcia, Guadalupe C., Bartol, Thomas M., Lee, Christopher T., Khandelwal, Priya, Liu, Emily, Spencer, Donald J., Husar, Adam, Bushong, Eric A., Phan, Sebastien, Perkins, Guy, Ellisman, Mark H., Skupin, Alexander, Sejnowski, Terrence J., Rangamani, Padmini
Format: Journal Article
Language:English
Published: United States Wiley Subscription Services, Inc 01-04-2022
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Summary:In the highly dynamic metabolic landscape of a neuron, mitochondrial membrane architectures can provide critical insight into the unique energy balance of the cell. Current theoretical calculations of functional outputs like adenosine triphosphate and heat often represent mitochondria as idealized geometries, and therefore, can miscalculate the metabolic fluxes. To analyze mitochondrial morphology in neurons of mouse cerebellum neuropil, 3D tracings of complete synaptic and axonal mitochondria were constructed using a database of serial transmission electron microscopy (TEM) tomography images and converted to watertight meshes with minimal distortion of the original microscopy volumes with a granularity of 1.64 nanometer isotropic voxels. The resulting in‐silico representations were subsequently quantified by differential geometry methods in terms of the mean and Gaussian curvatures, surface areas, volumes, and membrane motifs, all of which can alter the metabolic output of the organelle. Finally, we identify structural motifs present across this population of mitochondria, which may contribute to future modeling studies of mitochondrial physiology and metabolism in neurons. High quality 3D reconstructions of mitochondria were generated using serial TEM tomography images of axonal and presynaptic mitochondria, producing minimal distortion from the original images. The resulting in‐silico representations were subsequently quantified by differential geometry methods in terms of curvatures, surface areas, volumes, and membrane motifs, all of which can alter the metabolic output of the organelle. These methods enable structural motifs to be identified across the sampled population, presenting useful information for future physiological modeling of neuronal mitochondria.
Bibliography:These authors contributed equally to this work.
These authors also contributed equally to this work.
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AUTHOR CONTRIBUTIONS
R.M., G.C.G., T.M.B., C.T.L., G.P., M.E., A.S.,T.J.S., and P.R. conceived and designed the research. E.B. prepared the specimen. S.P. performed the tomography. G.P. and M.H.E. worked with E.B. and S.P. on EM. R.M., G.C.G., E.L., P.K., D.J.S., and T.M.B. performed the reconstructions. A.H., T.M.B., G.C.G., and C.T.L. developed software. G.C.G., R.M., T.M.B., T.J.S., and P.R. analyzed the data. G.C.G., R.M., T.M.B., C.T.L., D.J.S., A.S., T.J.S., and P.R. wrote the paper. All authors agree on the contents of the manuscript.
ISSN:0021-9967
1096-9861
DOI:10.1002/cne.25254