Morphological principles of neuronal mitochondria.
Rachel MendelsohnGuadalupe C GarciaThomas M BartolChristopher T LeePriya KhandelwalEmily LiuDonald J SpencerAdam HusarEric A BushongSebastien PhanGuy PerkinsMark H EllismanAlexander SkupinTerrence J SejnowskiPadmini RangamaniPublished in: The Journal of comparative neurology (2021)
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.
Keyphrases
- electron microscopy
- oxidative stress
- cell death
- endoplasmic reticulum
- reactive oxygen species
- single cell
- spinal cord
- optical coherence tomography
- high resolution
- molecular dynamics
- density functional theory
- deep learning
- spinal cord injury
- cell therapy
- protein kinase
- wastewater treatment
- emergency department
- brain injury
- mesenchymal stem cells
- working memory
- single molecule
- convolutional neural network
- current status
- molecular dynamics simulations
- high throughput