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Lookup NU author(s): Dr Amy VincentORCiD, Dr Kathryn White, Tracey DaveyORCiD, Jonathan Phillips, Dr Conor LawlessORCiD, Charlotte Warren, Dr Yi NgORCiD, Gavin Falkous, Tom Holden, Professor David Deehan, Professor Robert Taylor, Emeritus Professor Doug Turnbull, Dr Martin Picard
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Genetic and biochemical defects of mitochondrial function are a major cause of human disease, but their link to mitochondrial morphology in situ has not been defined. Here, we develop a quantitative three-dimensional approach to map mitochondrial network organization in human muscle at electron microscopy resolution. We establish morphological differences between human and mouse and among patients with mitochondrial DNA (mtDNA) diseases compared to healthy controls. We also define the ultrastructure and prevalence of mitochondrial nanotunnels, which exist as either free-ended or connecting membrane protrusions across non-adjacent mitochondria. A multivariate model integrating mitochondrial volume, morphological complexity, and branching anisotropy computed across individual mitochondria and mitochondrial populations identifies increased proportion of simple mitochondria and nanotunnels as a discriminant signature of mitochondrial stress. Overall, these data define the nature of the mitochondrial network in human muscle, quantify human-mouse differences, and suggest potential morphological markers
Author(s): Vincent AE, White K, Davey T, Philips J, Ogden RT, Lawless C, Warren C, Hall MG, Ng YS, Falkous G, Holden T, Deehan D, Taylor RW, Turnbull DM, Picard M
Publication type: Article
Publication status: Published
Journal: Cell Reports
Year: 2019
Volume: 26
Issue: 4
Pages: 996-1009.e4
Print publication date: 22/01/2019
Online publication date: 14/01/2019
Acceptance date: 02/01/2019
Date deposited: 15/01/2019
ISSN (electronic): 2211-1247
Publisher: Cell Press
URL: https://doi.org/10.1016/j.celrep.2019.01.010
DOI: 10.1016/j.celrep.2019.01.010
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