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Quantiative 3D Mapping of The Human Skeletal Muscle Mitochondrial Network

Lookup NU author(s): Dr Amy Vincent, Dr Kathryn White, Tracey Davey, Jonathan Phillips, Dr Conor Lawless, Charlotte Warren, Dr Yi Ng, Gavin Falkous, Tom Holden, Professor David Deehan, Professor Robert Taylor, Professor Doug Turnbull, Dr Martin Picard

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

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


Publication metadata

Author(s): Vincent AE, White K, Davey T, Philips J, Ogden RT, Lawess 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: 99-1009.e4

Print publication date: 22/01/2019

Online publication date: 15/01/2019

Acceptance date: 02/01/2019

ISSN (electronic): 2211-1247

Publisher: Elsevier

URL: https://doi.org/10.1016/j.celrep.2019.01.010

DOI: 10.1016/j.celrep.2019.01.010


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