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Beyond the unwinding: Role of TOP1MT in mitochondrial translation

Baechler, SA; Dalla Rosa, I; Spinazzola, A; Pommier, Y; (2019) Beyond the unwinding: Role of TOP1MT in mitochondrial translation. Cell Cycle , 18 (19) pp. 2377-2384. 10.1080/15384101.2019.1646563.

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Abstract

Mitochondria contain their own genome (mtDNA), encoding 13 proteins of the enzyme complexes of the oxidative phosphorylation. Synthesis of these 13 mitochondrial proteins requires a specific translation machinery, the mitoribosomes whose RNA components are encoded by the mtDNA, whereas more than 80 proteins are encoded by nuclear genes. It has been well established that mitochondrial topoisomerase I (TOP1MT) is important for mtDNA integrity and mitochondrial transcription as it prevents excessive mtDNA negative supercoiling and releases topological stress during mtDNA replication and transcription. We recently showed that TOP1MT also supports mitochondrial protein synthesis, and thus is critical for promoting tumor growth. Impaired mitochondrial protein synthesis leads to activation of the mitonuclear stress response through the transcription factor ATF4, and induces cytoprotective genes in order to prevent mitochondrial and cellular dysfunction. In this perspective, we highlight the novel role of TOP1MT in mitochondrial protein synthesis and as potential target for chemotherapy.

Type: Article
Title: Beyond the unwinding: Role of TOP1MT in mitochondrial translation
Location: United States
DOI: 10.1080/15384101.2019.1646563
Publisher version: https://doi.org/10.1080/15384101.2019.1646563
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Cancer, mitochondria, mitochondrial targeted therapy, mitochondrial topoisomerase I, mitochondrial translation, mitoribosome
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 Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences
URI: https://discovery.ucl.ac.uk/id/eprint/10078979
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