UCL logo

UCL Discovery

UCL home » Library Services » Electronic resources » UCL Discovery

Quantitative 3D Mapping of the Human Skeletal Muscle Mitochondrial Network

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. Green open access

[img]
Preview
Text
1-s2.0-S221112471930018X-main.pdf - ["content_typename_Published version" not defined]

Download (5MB) | Preview

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 > Provost and Vice Provost Offices
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 Pop Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > UCL GOS Institute of Child Health > ICH Developmental Neurosciences Prog
URI: http://discovery.ucl.ac.uk/id/eprint/10069421
Downloads since deposit
42Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item