Evaluation of endpoints for the study and diagnosis of mitochondrial toxicity and disease: a narrative review

Gharti, Pash; Fletcher, Jessica; Chapman, Katherine

doi:10.1093/mutage/gead010

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Evaluation of endpoints for the study and diagnosis of mitochondrial toxicity and disease: a narrative review

Pash Gharti, Jessica Fletcher

, Katherine Chapman

Mutagenesis, Volume: 38, Issue: 3

Swansea University Authors: Pash Gharti, Jessica Fletcher , Katherine Chapman

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DOI (Published version): 10.1093/mutage/gead010

Abstract

Mitochondrial DNA mutation and toxicity have been linked to several inherited and acquired diseases; however, these are challenging to diagnose and characterize due to clinical and genetic heterogeneity. This review investigates current techniques for the analysis of mitochondrial perturbations, and...

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Published in:	Mutagenesis
ISSN:	0267-8357 1464-3804
Published:	Oxford University Press (OUP) 2023
Online Access:	Check full text
URI:	https://cronfa.swan.ac.uk/Record/cronfa63343
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spelling	v2 63343 2023-05-03 Evaluation of endpoints for the study and diagnosis of mitochondrial toxicity and disease: a narrative review d5dd05587c965ecb2d1b0466af6bf5e2 Pash Gharti Pash Gharti true false 25b51eb7a9fb4c1779b6b4b3a7ac3f1d 0000-0002-4911-2711 Jessica Fletcher Jessica Fletcher true false 19e7d85eec17117858d867ec0c9f575e 0000-0001-6668-0705 Katherine Chapman Katherine Chapman true false 2023-05-03 MRKT Mitochondrial DNA mutation and toxicity have been linked to several inherited and acquired diseases; however, these are challenging to diagnose and characterize due to clinical and genetic heterogeneity. This review investigates current techniques for the analysis of mitochondrial perturbations, and novel, emerging endpoints for routine application within the clinical setting. Particular focus is given to the biochemistry of the mitochondria influencing each endpoint and the relation of these to toxicity. Current approaches such as the use of metabolic markers (e.g. lactate production), and muscle biopsies to measure mitochondrial proteins were found to lack specificity. Newly emerging identified endpoints were: fibroblast growth factor-21, glucose uptake, mitochondrial membrane potential, mitochondrial morphology, mtDNA heteroplasmy, and mutation of mtDNA and nuclear DNA. Owed to the advancement in genetic analysis techniques, it is suggested by this review that genotypic endpoints of mtDNA mutation and heteroplasmy show particular promise as indicators of mitochondrial disease. It is, however, acknowledged that any single endpoint in isolation offers limited information; therefore, it is recommended that analysis of several endpoints simultaneously will offer the greatest benefit in terms of disease diagnosis and study. It is hoped that this review further highlights the need for advancement in understanding mitochondrial disease. Journal Article Mutagenesis 38 3 Oxford University Press (OUP) 0267-8357 1464-3804 5 5 2023 2023-05-05 10.1093/mutage/gead010 http://dx.doi.org/10.1093/mutage/gead010 COLLEGE NANME Marketing COLLEGE CODE MRKT Swansea University SU Library paid the OA fee (TA Institutional Deal) Swansea University 2023-08-31T11:15:34.5060788 2023-05-03T16:21:18.0463450 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Pash Gharti 1 Jessica Fletcher 0000-0002-4911-2711 2 Katherine Chapman 0000-0001-6668-0705 3 63343__28079__00585b18182d41939686797a14fb1e0f.pdf 63343.pdf 2023-07-11T13:56:34.7449616 Output 219060 application/pdf Version of Record true This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. true eng https://creativecommons.org/licenses/by/4.0/
title	Evaluation of endpoints for the study and diagnosis of mitochondrial toxicity and disease: a narrative review
spellingShingle	Evaluation of endpoints for the study and diagnosis of mitochondrial toxicity and disease: a narrative review Pash Gharti Jessica Fletcher Katherine Chapman
title_short	Evaluation of endpoints for the study and diagnosis of mitochondrial toxicity and disease: a narrative review
title_full	Evaluation of endpoints for the study and diagnosis of mitochondrial toxicity and disease: a narrative review
title_fullStr	Evaluation of endpoints for the study and diagnosis of mitochondrial toxicity and disease: a narrative review
title_full_unstemmed	Evaluation of endpoints for the study and diagnosis of mitochondrial toxicity and disease: a narrative review
title_sort	Evaluation of endpoints for the study and diagnosis of mitochondrial toxicity and disease: a narrative review
author_id_str_mv	d5dd05587c965ecb2d1b0466af6bf5e2 25b51eb7a9fb4c1779b6b4b3a7ac3f1d 19e7d85eec17117858d867ec0c9f575e
author_id_fullname_str_mv	d5dd05587c965ecb2d1b0466af6bf5e2_*_Pash Gharti 25b51eb7a9fb4c1779b6b4b3a7ac3f1d__Jessica Fletcher 19e7d85eec17117858d867ec0c9f575e_**_Katherine Chapman
author	Pash Gharti Jessica Fletcher Katherine Chapman
author2	Pash Gharti Jessica Fletcher Katherine Chapman
format	Journal article
container_title	Mutagenesis
container_volume	38
container_issue	3
publishDate	2023
institution	Swansea University
issn	0267-8357 1464-3804
doi_str_mv	10.1093/mutage/gead010
publisher	Oxford University Press (OUP)
college_str	Faculty of Medicine, Health and Life Sciences
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hierarchy_top_title	Faculty of Medicine, Health and Life Sciences
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hierarchy_parent_title	Faculty of Medicine, Health and Life Sciences
department_str	Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
url	http://dx.doi.org/10.1093/mutage/gead010
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description	Mitochondrial DNA mutation and toxicity have been linked to several inherited and acquired diseases; however, these are challenging to diagnose and characterize due to clinical and genetic heterogeneity. This review investigates current techniques for the analysis of mitochondrial perturbations, and novel, emerging endpoints for routine application within the clinical setting. Particular focus is given to the biochemistry of the mitochondria influencing each endpoint and the relation of these to toxicity. Current approaches such as the use of metabolic markers (e.g. lactate production), and muscle biopsies to measure mitochondrial proteins were found to lack specificity. Newly emerging identified endpoints were: fibroblast growth factor-21, glucose uptake, mitochondrial membrane potential, mitochondrial morphology, mtDNA heteroplasmy, and mutation of mtDNA and nuclear DNA. Owed to the advancement in genetic analysis techniques, it is suggested by this review that genotypic endpoints of mtDNA mutation and heteroplasmy show particular promise as indicators of mitochondrial disease. It is, however, acknowledged that any single endpoint in isolation offers limited information; therefore, it is recommended that analysis of several endpoints simultaneously will offer the greatest benefit in terms of disease diagnosis and study. It is hoped that this review further highlights the need for advancement in understanding mitochondrial disease.
published_date	2023-05-05T11:15:34Z
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Evaluation of endpoints for the study and diagnosis of mitochondrial toxicity and disease: a narrative review

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