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Lookup NU author(s): Julie Faitg, Tracey DaveyORCiD, Ross LawsORCiD, Dr Conor LawlessORCiD, Dr Helen Tuppen, Eric Fitton, Emeritus Professor Doug Turnbull, Dr Amy VincentORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2025. The Author(s). Mitochondria play a crucial role in maintaining cellular health. It is interesting that the shape of mitochondria can vary depending on the type of cell, mitochondrial function, and other cellular conditions. However, there are limited studies that link functional assessment with mitochondrial morphology evaluation at high magnification, even fewer that do so in situ and none in human muscle biopsies. Therefore, we have developed a method which combines functional assessment of mitochondria through Cytochrome c Oxidase (COX) histochemistry, with a 3D electron microscopy (EM) technique, serial block-face scanning electron microscopy (SBFSEM). Here we apply COX-SBFSEM to muscle samples from patients with single, large-scale mtDNA deletions, a cause of mitochondrial disease. These deletions cause oxidative phosphorylation deficiency, which can be observed through changes in COX activity. One of the main advantages of combining 3D-EM with the COX reaction is the ability to look at how per-mitochondrion oxidative phosphorylation status is spatially distributed within muscle fibres. Here we show a robust spatial pattern in COX-positive and intermediate-fibres and that the spatial pattern is less clear in COX-deficient fibres.
Author(s): Faitg J, Davey T, Laws R, Lawless C, Tuppen H, Fitton E, Turnbull D, Vincent AE
Publication type: Article
Publication status: Published
Journal: Communications Biology
Year: 2025
Volume: 8
Online publication date: 09/01/2025
Acceptance date: 09/12/2024
Date deposited: 27/01/2025
ISSN (electronic): 2399-3642
Publisher: Springer Nature
URL: https://doi.org/10.1038/s42003-024-07389-7
DOI: 10.1038/s42003-024-07389-7
Data Access Statement: All data, images and models are available on request. Numerical source data for all graphs in the manuscript can be found in Supplementary data file. Code available on github: https://github.com/AEVincent/Faitg-et-al or on Zenado.
PubMed id: 39789156
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