Aiestaran-Zelaia, I;
Sánchez-Guisado, MJ;
Villar-Fernandez, M;
Azkargorta, M;
Fadon-Padilla, L;
Fernandez-Pelayo, U;
Perez-Rodriguez, D;
... Holt, IJ; + view all
(2022)
2 deoxy-D-glucose augments the mitochondrial respiratory chain in heart.
Scientific Reports
, 12
(1)
, Article 6890. 10.1038/s41598-022-10168-1.
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Abstract
2-Deoxy-D-glucose (2DG) has recently received emergency approval for the treatment of COVID-19 in India, after a successful clinical trial. SARS-CoV-2 infection of cultured cells is accompanied by elevated glycolysis and decreased mitochondrial function, whereas 2DG represses glycolysis and stimulates respiration, and restricts viral replication. While 2DG has pleiotropic effects on cell metabolism in cultured cells it is not known which of these manifests in vivo. On the other hand, it is known that 2DG given continuously can have severe detrimental effects on the rodent heart. Here, we show that the principal effect of an extended, intermittent 2DG treatment on mice is to augment the mitochondrial respiratory chain proteome in the heart; importantly, this occurs without vacuolization, hypertrophy or fibrosis. The increase in the heart respiratory chain proteome suggests an increase in mitochondrial oxidative capacity, which could compensate for the energy deficit caused by the inhibition of glycolysis. Thus, 2DG in the murine heart appears to induce a metabolic configuration that is the opposite of SARS-CoV-2 infected cells, which could explain the compound's ability to restrict the propagation of the virus to the benefit of patients with COVID-19 disease.
| Type: | Article |
|---|---|
| Title: | 2 deoxy-D-glucose augments the mitochondrial respiratory chain in heart |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41598-022-10168-1 |
| Publisher version: | https://doi.org/10.1038/s41598-022-10168-1 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third-party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | Animals, COVID-19, Deoxyglucose, Electron Transport, Glucose, Humans, Mice, Proteome, SARS-CoV-2 |
| UCL classification: | 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 UCL 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/10148260 |
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