The DOI matches its Crossref record; 16 of the 16 references it cites were found in a registry or an index.
Nrf2 regulates ROS production by mitochondria and NADPH oxidase
Open accessAbstract
BACKGROUND: Nuclear factor (erythroid-derived 2) factor 2 (Nrf2) is a crucial transcription factor mediating protection against oxidants. Nrf2 is negatively regulated by cytoplasmic Kelch-like ECH associated protein 1 (Keap1) thereby providing inducible antioxidant defence. Antioxidant properties of Nrf2 are thought to be mainly exerted by stimulating transcription of antioxidant proteins, whereas its effects on ROS production within the cell are uncertain. METHODS: Live cell imaging and qPCR in brain hippocampal glio-neuronal cultures and explants slice cultures with graded expression of Nrf2, i.e. Nrf2-knockout (Nrf2-KO), wild-type (WT), and Keap1-knockdown (Keap1-KD). RESULTS: We here show that ROS production in Nrf2-KO cells and tissues is increased compared to their WT counterparts. Mitochondrial ROS production is regulated by the Keap1-Nrf2 pathway by controlling mitochondrial bioenergetics. Surprisingly, Keap1-KD cells and tissues also showed higher rates of ROS production when compared to WT, although with a smaller magnitude. Analysis of the mRNA expression levels of the two NOX isoforms implicated in brain pathology showed, that NOX2 is dramatically upregulated under conditions of Nrf2 deficiency, whereas NOX4 is upregulated when Nrf2 is constitutively activated (Keap1-KD) to a degree which paralleled the increases in ROS production. CONCLUSIONS: These observations suggest that the Keap1-Nrf2 pathway regulates both mitochondrial and cytosolic ROS production through NADPH oxidase. GENERAL SIGNIFICANCE: Findings supports a key role of the Keap1-Nrf2 pathway in redox homeostasis within the cell.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology
Bedard, K., & Krause, K.-H. (2007) · Physiological Reviews · doi:10.1152/physrev.00044.2005 · Cited by 6,989
Targeting the KEAP1-NRF2 system to prevent kidney disease progression
Nezu, M., Suzuki, N., & Yamamoto, M. (2017) · American Journal of Nephrology · doi:10.1159/000475890 · Cited by 3,447
Oxidative stress and neurodegeneration: where are we now?
Halliwell, B. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.03907.x · Cited by 2,614
Nrf2–Keap1 defines a physiologically important stress response mechanism
Motohashi, H., & Yamamoto, M. (2004) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2004.09.003 · Cited by 1,725 · cited 1×
“Nrf2 binds to antioxidant response elements (AREs), specific sequences present in the promoter regions of its target genes, as a heterodimer with a small Maf protein, and stimulates transcription of antioxidant proteins [4].”
BackgroundNrf2 Redirects Glucose and Glutamine into Anabolic Pathways in Metabolic Reprogramming
Mitsuishi, Y., Taguchi, K., Kawatani, Y., Shibata, T., Nukiwa, T., Aburatani, H., Yamamoto, M., & Motohashi, H. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.05.016 · Cited by 1,395
Linker, R. A., Lee, D.-H., Ryan, S., van Dam, A. M., Conrad, R., Bista, P., Zeng, W., Hronowsky, X., Buko, A., Chollate, S., et al. (2011) · Brain · doi:10.1093/brain/awq386 · Cited by 1,155
Wakabayashi, N., Dinkova-Kostova, A. T., Holtzclaw, W. D., Kang, M.-I., Kobayashi, A., Yamamoto, M., Kensler, T. W., & Talalay, P. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0307301101 · Cited by 986 · cited 1×
“However, this is consistent with the facts that: (i) inhibition of histone deacetylase (HDAC) 3 has been shown to decrease NOX4 transcription in human endothelial cells [33], (ii) similarly to other HDACs, HDAC3 is inactivated by oxidative stress [34], and (iii) compared to WT cells, the levels of GSH are lower in Nrf…”
ResultCucoranu, I., Clempus, R., Dikalova, A., Phelan, P. J., Ariyan, S., Dikalov, S., & Sorescu, D. (2005) · Circulation Research · doi:10.1161/01.res.0000187457.24338.3d · Cited by 786
Gandhi, S., Wood-Kaczmar, A., Yao, Z., Plun-Favreau, H., Deas, E., Klupsch, K., Downward, J., Latchman, D. S., Tabrizi, S. J., Wood, N. W., et al. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.02.013 · Cited by 682
Self-citationKleinschnitz, C., Grund, H., Wingler, K., Armitage, M. E., Jones, E., Mittal, M., Barit, D., Schwarz, T., Geis, C., Kraft, P., et al. (2010) · PLoS Biology · doi:10.1371/journal.pbio.1000479 · Cited by 447
Cited by
ROS, Cell Senescence, and Novel Molecular Mechanisms in Aging and Age‐Related Diseases
Davalli, P., Mitic, T., Caporali, A., Lauriola, A., & D’Arca, D. (2016) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/3565127 · Cited by 1,059
The emerging role of Nrf2 in mitochondrial function
Dinkova-Kostova, A. T., & Abramov, A. Y. (2015) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2015.04.036 · Cited by 983
Self-citationTebay, L. E., Robertson, H., Durant, S. T., Vitale, S. R., Penning, T. M., Dinkova-Kostova, A. T., & Hayes, J. D. (2015) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2015.06.021 · Cited by 837
Self-citationROS and redox signaling in myocardial ischemia-reperfusion injury and cardioprotection
Cadenas, S. (2018) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.01.024 · Cited by 820
Role of mitochondrial ROS in the brain: from physiology to neurodegeneration
Angelova, P. R., & Abramov, A. Y. (2018) · FEBS Letters · doi:10.1002/1873-3468.12964 · Cited by 789
Self-citation
Metadata
- Authors
- Kovac, S., Angelova, P. R., Holmström, K. M., Zhang, Y., Dinkova-Kostova, A. T., & Abramov, A. Y.
- Venue
- Biochimica et Biophysica Acta (BBA) - General Subjects
- Publisher
- Elsevier BV
- Published
- 2015-04
- Volume
- 1850
- Issue
- 4
- Pages
- 794-801
- ISSN
- 0304-4165 (ISSN-L)
- OpenAlex
- W2064327102
- Cited by
- 604
- References
- 16
- FWCI
- 11.80
- Type
- journal article
- Language
- en
- Open access
- hybrid
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Nrf2 regulates ROS production by mitochondria and NADPH oxidase. https://app.cochat.ai/papers/10.1016/j.bbagen.2014.11.021
- The paper
- Kovac, S., Angelova, P. R., Holmström, K. M., Zhang, Y., Dinkova-Kostova, A. T., & Abramov, A. Y. (2015). Nrf2 regulates ROS production by mitochondria and NADPH oxidase. Biochimica et Biophysica Acta (BBA) - General Subjects. https://doi.org/10.1016/j.bbagen.2014.11.021
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
