Evidence map›Paper›PMID 36893757›Full record

ArticleMolecular cell2023

Oxygen toxicity causes cyclic damage by destabilizing specific Fe-S cluster-containing protein complexes.

Alan H Baik, Augustinus G Haribowo, Xuewen Chen, Bruno B Queliconi, Alec M Barrios, Ankur Garg, Mazharul Maishan, Alexandre R Campos, Michael A Matthay, Isha H Jain

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
6.6field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

35 citing papers in PubMed, 43 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Review
  5. Article
  6. Bench evidence, bedside uncertainty: hyperoxia, mechanical ventilation and lung injury.European respiratory review : an official journal of the European Respiratory Society · 2026
    Review
  7. Article
  8. Review
  9. Review
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  11. Review
  12. Review
  13. Power and poison: The intersections of HThe Journal of biological chemistry · 2025
    Review
  14. Article
  15. Article
  16. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 1 country.

Alan H BaikDepartment of Medicine, Division of Cardiology, University of California, San Francisco, San Francisco, CA 94143, USA; Gladstone Institutes, San Francisco, CA 94158, USA.
Augustinus G HaribowoGladstone Institutes, San Francisco, CA 94158, USA; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.
Xuewen ChenGladstone Institutes, San Francisco, CA 94158, USA; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA; Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA.
Bruno B QueliconiGladstone Institutes, San Francisco, CA 94158, USA; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.
Alec M BarriosGladstone Institutes, San Francisco, CA 94158, USA; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.
Ankur GargGladstone Institutes, San Francisco, CA 94158, USA; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.
Mazharul MaishanCardiovascular Research Institute, UCSF, San Francisco, CA 94143, USA.
Alexandre R CamposSanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
Michael A MatthayCardiovascular Research Institute, UCSF, San Francisco, CA 94143, USA; Departments of Medicine and Anesthesia, University of California, San Francisco, San Francisco, CA 94143, USA.
Isha H JainGladstone Institutes, San Francisco, CA 94158, USA; Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: isha.jain@gladstone.ucsf.edu.
Gladstone Institutes · USUniversity of California, San Francisco · USSanford Burnham Prebys Medical Discovery Institute · US

Funding

Tumor Microenvironment and Cancer ImmunologyP30CA030199 · NCI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI Jianhua Zhao · 1985 to 2026
$107.2M
MOLECULAR AND CELLULAR BASIS OF CARDIOVASCULAR DISEASET32HL007731 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Brian L Black · 1992 to 2026
$12.4M
Redesigning a Neuron's Breath: A Modern Twist to Classical Oxygen BiologyDP5OD026398 · OD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JAIN, ISHA HIMANI · 2018 to 2022
$2.2M
NCI NIH HHS P30 CA030199NHLBI NIH HHS T32 HL007731NIH HHS DP5 OD026398
6 · The paper itself

Abstract

Oxygen is toxic across all three domains of life. Yet, the underlying molecular mechanisms remain largely unknown. Here, we systematically investigate the major cellular pathways affected by excess molecular oxygen. We find that hyperoxia destabilizes a specific subset of Fe-S cluster (ISC)-containing proteins, resulting in impaired diphthamide synthesis, purine metabolism, nucleotide excision repair, and electron transport chain (ETC) function. Our findings translate to primary human lung cells and a mouse model of pulmonary oxygen toxicity. We demonstrate that the ETC is the most vulnerable to damage, resulting in decreased mitochondrial oxygen consumption. This leads to further tissue hyperoxia and cyclic damage of the additional ISC-containing pathways. In support of this model, primary ETC dysfunction in the Ndufs4 KO mouse model causes lung tissue hyperoxia and dramatically increases sensitivity to hyperoxia-mediated ISC damage. This work has important implications for hyperoxia pathologies, including bronchopulmonary dysplasia, ischemia-reperfusion injury, aging, and mitochondrial disorders.

Indexed as

HyperoxiaMitochondrial DiseasesAnimalsElectron Transport Complex IHumansLungMiceMitochondriaOxygenElectron Transport Complex INdufs4 protein, mouseOxygenDNA damageFe-S clustershyperoxialung injurymitochondriaoxygenpurine synthesisredoxtranslation fidelity

Identifiers

PMID36893757
PMCPMC10148707
OpenAlexW4323543763

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.