Rev1 deficiency induces a metabolic shift in MEFs that can be manipulated by the NAD+ precursor nicotinamide riboside

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Rev1 deficiency induces a metabolic shift in MEFs that can be manipulated by the NAD+ precursor nicotinamide riboside. / Anugula, Sharath; Li, Zhiquan; Li, Yuan; Hendriksen, Alexander; Christensen, Peter Bjarn; Wang, Lin; Monk, Jonathan M.; de Wind, Niels; Bohr, Vilhelm A.; Desler, Claus; Naviaux, Robert K.; Rasmussen, Lene Juel.

In: Heliyon, Vol. 9, No. 6, e17392, 2023.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Anugula, S, Li, Z, Li, Y, Hendriksen, A, Christensen, PB, Wang, L, Monk, JM, de Wind, N, Bohr, VA, Desler, C, Naviaux, RK & Rasmussen, LJ 2023, 'Rev1 deficiency induces a metabolic shift in MEFs that can be manipulated by the NAD+ precursor nicotinamide riboside', Heliyon, vol. 9, no. 6, e17392. https://doi.org/10.1016/j.heliyon.2023.e17392

APA

Anugula, S., Li, Z., Li, Y., Hendriksen, A., Christensen, P. B., Wang, L., Monk, J. M., de Wind, N., Bohr, V. A., Desler, C., Naviaux, R. K., & Rasmussen, L. J. (2023). Rev1 deficiency induces a metabolic shift in MEFs that can be manipulated by the NAD+ precursor nicotinamide riboside. Heliyon, 9(6), [e17392]. https://doi.org/10.1016/j.heliyon.2023.e17392

Vancouver

Anugula S, Li Z, Li Y, Hendriksen A, Christensen PB, Wang L et al. Rev1 deficiency induces a metabolic shift in MEFs that can be manipulated by the NAD+ precursor nicotinamide riboside. Heliyon. 2023;9(6). e17392. https://doi.org/10.1016/j.heliyon.2023.e17392

Author

Anugula, Sharath ; Li, Zhiquan ; Li, Yuan ; Hendriksen, Alexander ; Christensen, Peter Bjarn ; Wang, Lin ; Monk, Jonathan M. ; de Wind, Niels ; Bohr, Vilhelm A. ; Desler, Claus ; Naviaux, Robert K. ; Rasmussen, Lene Juel. / Rev1 deficiency induces a metabolic shift in MEFs that can be manipulated by the NAD+ precursor nicotinamide riboside. In: Heliyon. 2023 ; Vol. 9, No. 6.

Bibtex

@article{41e13caff28840648077c50618a22283,
title = "Rev1 deficiency induces a metabolic shift in MEFs that can be manipulated by the NAD+ precursor nicotinamide riboside",
abstract = "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.",
keywords = "Autophagy, Healthspan, Mitochondria, NAD, Nicotinamide riboside, Replication stress, Rev1",
author = "Sharath Anugula and Zhiquan Li and Yuan Li and Alexander Hendriksen and Christensen, {Peter Bjarn} and Lin Wang and Monk, {Jonathan M.} and {de Wind}, Niels and Bohr, {Vilhelm A.} and Claus Desler and Naviaux, {Robert K.} and Rasmussen, {Lene Juel}",
note = "Publisher Copyright: {\textcopyright} 2023 The Authors",
year = "2023",
doi = "10.1016/j.heliyon.2023.e17392",
language = "English",
volume = "9",
journal = "Heliyon",
issn = "2405-8440",
publisher = "Elsevier",
number = "6",

}

RIS

TY - JOUR

T1 - Rev1 deficiency induces a metabolic shift in MEFs that can be manipulated by the NAD+ precursor nicotinamide riboside

AU - Anugula, Sharath

AU - Li, Zhiquan

AU - Li, Yuan

AU - Hendriksen, Alexander

AU - Christensen, Peter Bjarn

AU - Wang, Lin

AU - Monk, Jonathan M.

AU - de Wind, Niels

AU - Bohr, Vilhelm A.

AU - Desler, Claus

AU - Naviaux, Robert K.

AU - Rasmussen, Lene Juel

N1 - Publisher Copyright: © 2023 The Authors

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

KW - Autophagy

KW - Healthspan

KW - Mitochondria

KW - NAD

KW - Nicotinamide riboside

KW - Replication stress

KW - Rev1

U2 - 10.1016/j.heliyon.2023.e17392

DO - 10.1016/j.heliyon.2023.e17392

M3 - Journal article

C2 - 37484291

AN - SCOPUS:85162171902

VL - 9

JO - Heliyon

JF - Heliyon

SN - 2405-8440

IS - 6

M1 - e17392

ER -

ID: 358559758