2 deoxy-D-glucose augments the mitochondrial respiratory chain in heart.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
27 04 2022
27 04 2022
Historique:
received:
01
09
2021
accepted:
22
03
2022
entrez:
28
4
2022
pubmed:
29
4
2022
medline:
30
4
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 35478201
doi: 10.1038/s41598-022-10168-1
pii: 10.1038/s41598-022-10168-1
pmc: PMC9044724
doi:
Substances chimiques
Proteome
0
Deoxyglucose
9G2MP84A8W
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6890Subventions
Organisme : Medical Research Council
ID : MC_PC_13029/2
Pays : United Kingdom
Informations de copyright
© 2022. The Author(s).
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