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Quantitative 3D Mapping of the Human Skeletal Muscle Mitochondrial Network

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

Publication metadata

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


DOI: 10.1016/j.celrep.2019.01.010


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Funder referenceFunder name
203105/Z/16/ZWellcome Trust
BB/M012093/1Biotechnology and Biological Sciences Research Council (BBSRC)
MR/K000608/1Medical Research Council (MRC)
MR/L016354/1Medical Research Council (MRC)