The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
Activation of Mitochondrial Biogenesis by Heme Oxygenase-1–mediated NF-E2–related Factor-2 Induction Rescues Mice from Lethal Staphylococcus aureus Sepsis
Open accessAbstract
RATIONALE: Mitochondrial damage is an important component of multiple organ failure syndrome, a highly lethal complication of severe sepsis that lacks specific therapy. Mitochondrial quality control is regulated in part by the heme oxygenase-1 (HO-1; Hmox1) system through the redox-regulated NF-E2-related factor-2 (Nrf2) transcription factor, but its role in mitochondrial biogenesis in Staphylococcus aureus sepsis is unknown. OBJECTIVES: To test the hypothesis that Nrf2-dependent up-regulation of the HO-1/carbon monoxide (CO) system would preserve mitochondrial biogenesis and rescue mice from lethal S. aureus sepsis. METHODS: A controlled murine S. aureus peritonitis model with and without inhaled CO was examined for HO-1 and Nrf2 regulation of mitochondrial biogenesis and the resolution of hepatic mitochondrial damage. MEASUREMENTS AND MAIN RESULTS: Sepsis survival was significantly enhanced using inhaled CO (250 ppm once-daily for 1 h), and linked mechanistically to Hmox1 induction and mitochondrial HO activity through Nrf2 transcriptional and Akt kinase activity. HO-1/CO stimulated Nrf2-dependent gene expression and nuclear accumulation of nuclear respiratory factor-1, -2α (Gabpa), and peroxisome proliferator-activated receptor gamma coactivator-1α; increased mitochondrial transcription factor-A and citrate synthase protein levels; and augmented mtDNA copy number. CO enhanced antiinflammatory IL-10 and reduced proinflammatory tumor necrosis factor-α production. By contrast, Nrf2(-/-) and Akt1(-/-) mice lacked CO induction of Hmox1 and mitochondrial biogenesis, and CO rescued neither strain from S. aureus sepsis. CONCLUSIONS: We identify an inducible Nrf2/HO-1 regulatory cycle for mitochondrial biogenesis that is prosurvival and counter-inflammatory in sepsis, and describe targeted induction of mitochondrial biogenesis as a potential multiple organ failure therapy.
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 epidemiology of sepsis in the United States from 1979 through 2000
Martin, G. S., Mannino, D. M., Eaton, S., & Moss, M. (2003) · New England Journal of Medicine · doi:10.1056/nejmoa022139 · Cited by 5,841
Itoh, K., Wakabayashi, N., Katoh, Y., Ishii, T., Igarashi, K., Engel, J. D., & Yamamoto, M. (1999) · Genes & Development · doi:10.1101/gad.13.1.76 · Cited by 3,634
Reactive oxygen species, cellular redox systems, and apoptosis
Circu, M. L., & Aw, T. Y. (2010) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2009.12.022 · Cited by 3,340
Dinkova-Kostova, A. T., Holtzclaw, W. D., Cole, R. N., Itoh, K., Wakabayashi, N., Katoh, Y., Yamamoto, M., & Talalay, P. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.172398899 · Cited by 1,947
Transcriptional paradigms in mammalian mitochondrial biogenesis and function
Scarpulla, R. C. (2008) · Physiological Reviews · doi:10.1152/physrev.00025.2007 · Cited by 1,666
Nrf2 is a critical regulator of the innate immune response and survival during experimental sepsis
Thimmulappa, R. K. (2006) · Journal of Clinical Investigation · doi:10.1172/jci25790 · Cited by 1,028 · cited 1×
“Nrf2 also influences the innate immune response and survival in cecal ligation and puncture (27) and modulates leukocyte function in sepsis (28).”
BackgroundMolecular targets of oxidative stress
Avery, S. V. (2011) · Biochemical Journal · doi:10.1042/bj20101695 · Cited by 474
PGAM5 tethers a ternary complex containing Keap1 and Nrf2 to mitochondria
Lo, S.-C., & Hannink, M. (2008) · Experimental Cell Research · doi:10.1016/j.yexcr.2008.02.014 · Cited by 300
Zhang, X., Shan, P., Alam, J., Fu, X.-Y., & Lee, P. J. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m408092200 · Cited by 198
Suliman, H. B., Carraway, M. S., Welty-Wolf, K. E., Whorton, A. R., & Piantadosi, C. A. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m304719200 · Cited by 189
Self-citation
Cited by
Intercellular mitochondrial transfer as a means of tissue revitalization
Liu, D., Gao, Y., Liu, J., Huang, Y., Yin, J., Feng, Y., Shi, L., Meloni, B. P., Zhang, C., Zheng, M., et al. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00440-z · Cited by 403
Xiong, J., Wang, K., Yuan, C., Xing, R., Ni, J., Hu, G., Chen, F., & Wang, X. (2017) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2016.2809 · Cited by 120
van Dijk, M. C., de Kruijff, R. M., & Hagedoorn, P.-L. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.857237 · Cited by 41
Metadata
- Authors
- MacGarvey, N. C., Suliman, H. B., Bartz, R. R., Fu, P., Withers, C. M., Welty-Wolf, K. E., & Piantadosi, C. A.
- Venue
- American Journal of Respiratory and Critical Care Medicine
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-04-15
- Volume
- 185
- Issue
- 8
- Pages
- 851-861
- ISSN
- 1073-449X (ISSN-L)
- 1535-4970
- OpenAlex
- W2072207999
- Cited by
- 184
- References
- 10
- FWCI
- 6.04
- Type
- journal article
- Language
- en
- Open access
- green
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: Activation of Mitochondrial Biogenesis by Heme Oxygenase-1–mediated NF-E2–related Factor-2 Induction Rescues Mice from Lethal Staphylococcus aureus Sepsis. https://app.cochat.ai/papers/10.1164/rccm.201106-1152oc
- The paper
- MacGarvey, N. C., Suliman, H. B., Bartz, R. R., Fu, P., Withers, C. M., Welty-Wolf, K. E., & Piantadosi, C. A. (2012). Activation of Mitochondrial Biogenesis by Heme Oxygenase-1–mediated NF-E2–related Factor-2 Induction Rescues Mice from Lethal Staphylococcus aureus Sepsis. American Journal of Respiratory and Critical Care Medicine. https://doi.org/10.1164/rccm.201106-1152oc
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.
