Abstract
The cytoskeletal architecture directly affects the morphology, motility, and tensional homeostasis of the cell. In addition, the cytoskeleton is important for mitosis, intracellular traffic, organelle motility, and even cellular respiration. The organelle responsible for a majority of the energy conversion for the cell, the mitochondrion, has a dependence on the cytoskeleton for mobility and function. In previous studies, we established that cytoskeletal inhibitors altered the movement of the mitochondria, their morphology, and their respiration in human dermal fibroblasts. Here, we use this protocol to investigate applicability of power law diffusion to describe mitochondrial locomotion, assessment of rates of fission and fusion in healthy and diseased cells, and differences in mitochondria locomotion in more open networks either in response to cytoskeletal destabilizers or by cell line. We found that mitochondria within fibrosarcoma cells and within fibroblast cells treated with an actin-destabilizing toxin resulted in increased net travel, increased average velocity, and increased diffusion of mitochondria when compared to control fibroblasts. Although the mitochondria within the fibrosarcoma travel further than mitochondria within their healthy counterparts, fibroblasts, the dependence on mitochondria for respiration is much lower with higher rates ofhydrogen peroxide production and was confirmed using the OROBOROS O2K. We also found that rates of fission and fusion of the mitochondria equilibrate despite significant alteration of the cytoskeleton. Rates ranged from 15% to 25%, where the highest rates were observed within the fibrosarcoma cell line. This result is interesting because the fibrosarcoma cell line does not have increased respiration metrics including when compared to fibroblast. Mitochondria travel further, faster, and have an increase in percent mitochondria splitting or joining while not dependent on the mitochondria for a majority of its energy production. This study illustrates the complex interaction between mitochondrial movement and respiration through the disruption of the cytoskeleton.
Document Type
Article
Publication Date
12-15-2017
Digital Object Identifier (DOI)
https://doi.org/10.1242/bio.029009
Funding Information
This work was supported by the National Heart, Lung, and Blood Institute (K12 HL109009 to D.H.J.), the Office of Naval Research (N000141612100 to D.M.E.) and the University of Pennsylvania Department of Emergency Medicine (start-up funding to D.H.J.).
Related Content
Supplementary information available online at http://bio.biologists.org/lookup/doi/10.1242/bio.029009.supplemental
Repository Citation
Jang, David H.; Seeger, Sarah C.; Grady, Martha E.; Shofer, Frances S.; and Eckmann, David M., "Mitochondrial Dynamics and Respiration Within Cells with Increased Open Pore Cytoskeletal Meshes" (2017). Mechanical Engineering Faculty Publications. 32.
https://uknowledge.uky.edu/me_facpub/32
Supplementary information
Notes/Citation Information
Published in Biology Open, v. 6, issue 12, p. 1831-1839.
© 2017. Published by The Company of Biologists Ltd
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.