Rev1 deficiency induces a metabolic shift in MEFs that can be manipulated by the NAD+ precursor nicotinamide riboside
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Dokumenter
- Fulltext
Forlagets udgivne version, 6,18 MB, PDF-dokument
Replication stress, caused by Rev1 deficiency, is associated with mitochondrial dysfunction, and metabolic stress. However, the overall metabolic alterations and possible interventions to rescue the deficits due to Rev1 loss remain unclear. Here, we report that loss of Rev1 leads to intense changes in metabolites and that this can be manipulated by NAD + supplementation. Autophagy decreases in Rev1−/− mouse embryonic fibroblasts (MEFs) and can be restored by supplementing the NAD+ precursor nicotinamide riboside (NR). The abnormal mitochondrial morphology in Rev1−/− MEFs can be partially reversed by NR supplementation, which also protects the mitochondrial cristae from rotenone-induced degeneration. In nematodes rev-1 deficiency causes sensitivity to oxidative stress but this cannot be rescued by NR supplementation. In conclusion, Rev1 deficiency leads to metabolic dysregulation of especially lipid and nucleotide metabolism, impaired autophagy, and mitochondrial anomalies, and all of these phenotypes can be improved by NR replenishment in MEFs.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | e17392 |
| Tidsskrift | Heliyon |
| Vol/bind | 9 |
| Udgave nummer | 6 |
| ISSN | 2405-8440 |
| DOI | |
| Status | Udgivet - 2023 |
Bibliografisk note
Funding Information:
We thank the technical support for confocal microscopy and transmission electron microscope (TEM) at the Core Facility for Integrated Microscopy (CFIM) and that for FACS at the Flow Cytometry & Single Cell Core Facility at the Health and Medical Faculty at the University of Copenhagen . This work was supported by research grants from Nordea-fonden (L.J.R.), Olav Thon Foundation (L.J.R.), Novo Nordisk Foundation NNF17OC0027812 (L.J.R.). L.J.R. is a member of the Clinical Academic Group: Recovery Capacity After Acute Illness in An Aging Population (RECAP). We acknowledge support from the Intramural Program of the National Institute on Aging, National Institutes of Health , USA. Nicotinamide (NR) was obtained from Chromadex Corp ., which has a CRADA with Vilhelm Bohr. Support for the metabolomics studies was provided in part by the UCSD Christini Fund and the UCSD Mitochondrial Disease Research Fund.
Funding Information:
Dr Lene Juel Rasmussen was supported by Nordea-fonden, Olav Thon Stiftelsen, Novo Nordisk Fonden {NNF17OC0027812}.We thank the technical support for confocal microscopy and transmission electron microscope (TEM) at the Core Facility for Integrated Microscopy (CFIM) and that for FACS at the Flow Cytometry & Single Cell Core Facility at the Health and Medical Faculty at the University of Copenhagen. This work was supported by research grants from Nordea-fonden (L.J.R.), Olav Thon Foundation (L.J.R.), Novo Nordisk Foundation NNF17OC0027812 (L.J.R.). L.J.R. is a member of the Clinical Academic Group: Recovery Capacity After Acute Illness in An Aging Population (RECAP). We acknowledge support from the Intramural Program of the National Institute on Aging, National Institutes of Health, USA. Nicotinamide (NR) was obtained from Chromadex Corp. which has a CRADA with Vilhelm Bohr. Support for the metabolomics studies was provided in part by the UCSD Christini Fund and the UCSD Mitochondrial Disease Research Fund.
Funding Information:
Dr Lene Juel Rasmussen was supported by Nordea-fonden , Olav Thon Stiftelsen, Novo Nordisk Fonden { NNF17OC0027812 }.
Publisher Copyright:
© 2023 The Authors
Antal downloads er baseret på statistik fra Google Scholar og www.ku.dk
ID: 358559758