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See detailMorphological principles of neuronal mitochondria
Mendelsohn, Rachel; Garcia, Guadalupe C.; Bartol, Thomas M. et al

in Journal of Comparative Neurology (2022), 530(6), 886--902

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 ... [more ▼]

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. [less ▲]

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See detailMitochondrial morphology provides a mechanism for energy buffering at synapses
Garcia, Guadalupe Clara UL; Bartol, Thomas M.; Phan, Sebastien A. et al

E-print/Working paper (2019)

Mitochondria as the main energy suppliers of eukaryotic cells are highly dynamic organelles that fuse, divide and are transported along the cytoskeleton to ensure cellular energy homeostasis. While these ... [more ▼]

Mitochondria as the main energy suppliers of eukaryotic cells are highly dynamic organelles that fuse, divide and are transported along the cytoskeleton to ensure cellular energy homeostasis. While these processes are well established, substantial evidence indicates that the internal structure is also highly variable in dependence on metabolic conditions. However, a quantitative mechanistic understanding of how mitochondrial morphology affects energetic states is still elusive. To address this question, we here present an agent-based dynamic model using three-dimensional morphologies from electron microscopy tomography which considers the molecular dynamics of the main ATP production components. We apply our modeling approach to mitochondria at the synapse which is the largest energy consumer within the brain. Interestingly, comparing the spatiotemporal simulations with a corresponding space-independent approach, we find minor space dependence when the system relaxes toward equilibrium but a qualitative difference in fluctuating environments. These results suggest that internal mitochondrial morphology is not only optimized for ATP production but also provides a mechanism for energy buffering and may represent a mechanism for cellular robustness. [less ▲]

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See detailMitochondrial morphology provides a mechanism for energy buffering at synapses.
Garcia, Guadalupe Clara UL; Bartol, Thomas M.; Phan, Sébastien et al

in Scientific reports (2019), 9

Mitochondria as the main energy suppliers of eukaryotic cells are highly dynamic organelles that fuse, divide and are transported along the cytoskeleton to ensure cellular energy homeostasis. While these ... [more ▼]

Mitochondria as the main energy suppliers of eukaryotic cells are highly dynamic organelles that fuse, divide and are transported along the cytoskeleton to ensure cellular energy homeostasis. While these processes are well established, substantial evidence indicates that the internal structure is also highly variable in dependence on metabolic conditions. However, a quantitative mechanistic understanding of how mitochondrial morphology affects energetic states is still elusive. To address this question, we here present an agent-based multiscale model that integrates three-dimensional morphologies from electron microscopy tomography with the molecular dynamics of the main ATP producing components. We apply our modeling approach to mitochondria at the synapse which is the largest energy consumer within the brain. Interestingly, comparing the spatiotemporal simulations with a corresponding space-independent approach, we find minor spatial effects when the system relaxes toward equilibrium but a qualitative difference in fluctuating environments. These results suggest that internal mitochondrial morphology is not only optimized for ATP production but also provides a mechanism for energy buffering and may represent a mechanism for cellular robustness. IM [less ▲]

Detailed reference viewed: 97 (2 UL)