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Lookup NU author(s): Dr Katja Menger,
Alejandro Rodriguez Luis,
Dr James Chapman,
Dr Thomas Nicholls
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
The genome of mitochondria, called mtDNA, is a small circular DNA molecule present at thousands of copies per human cell. MtDNA is packaged into nucleoprotein complexes called nucleoids, and the density of mtDNA packaging affects mitochondrial gene expression. Genetic processes such as transcription, DNA replication and DNA packaging alter DNA topology, and these topological problems are solved by a family of enzymes called topoisomerases. Within mitochondria, topoisomerases are involved firstly in the regulation of mtDNA supercoiling and secondly in disentangling interlinked mtDNA molecules following mtDNA replication. The loss of mitochondrial topoisomerase activity leads to defects in mitochondrial function, and variants in the dual-localized type IA topoisomerase TOP3A have also been reported to cause human mitochondrial disease. We review the current knowledge on processes that alter mtDNA topology, how mtDNA topology is modulated by the action of topoisomerases, and the consequences of altered mtDNA topology for mitochondrial function and human health.
Author(s): Menger KE, Rodriguez-Luis A, Chapman J, Nicholls TJ
Publication type: Review
Publication status: Published
Journal: Open Biology
Online publication date: 22/09/2021
Acceptance date: 31/08/2021
ISSN (electronic): 2046-2441
PubMed id: 34547213