Vincent, AE;
White, K;
Davey, T;
Philips, J;
Ogden, RT;
Lawess, C;
Warren, C;
... Picard, M; + view all
(2019)
Quantitative 3D Mapping of the Human Skeletal Muscle Mitochondrial Network.
Cell Reports
, 26
(4)
996-1009.e4.
10.1016/j.celrep.2019.01.010.
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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 of mitochondrial dysfunction in human tissues.
| Type: | Article |
|---|---|
| Title: | Quantitative 3D Mapping of the Human Skeletal Muscle Mitochondrial Network |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.celrep.2019.01.010 |
| Publisher version: | https://doi.org/10.1016/j.celrep.2019.01.010 |
| Language: | English |
| Additional information: | © 2019 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/ 4.0/). |
| Keywords: | serial block-face SEM, reconstruction, mitochondrial disease; skeletal muscle; 3D morphometry; machine learning; mitochondrion; nanotunnel; reticulum; imaging |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Neurosciences Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10069421 |
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