Evidence map›Paper›PMID 35737799›Full record

ArticleScience (New York, N.Y.)2022

Tumor necrosis factor induces pathogenic mitochondrial ROS in tuberculosis through reverse electron transport.

Francisco J Roca, Laura J Whitworth, Hiran A Prag, Michael P Murphy, Lalita Ramakrishnan

Open access · hybridAbstract read
In one paragraph

Article in Science (New York, N.Y.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers.

0numbers the graph read from it
0cells of the map it votes in
102citing papers in PubMed
11.8field-weighted citation impact, top 1% 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

102 citing papers in PubMed, 152 citations in OpenAlex.

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  7. International journal of molecular sciences · 2026
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42 more citing papers are in PubMed but not listed here.

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

5 authors at 2 institutions in 1 country.

Francisco J RocaMolecular Immunity Unit, Cambridge Institute of Therapeutic Immunology and Infectious Diseases, Department of Medicine, University of Cambridge, Cambridge CB2 0AW, UK.ORCID 0000-0002-6744-148X
Laura J WhitworthMolecular Immunity Unit, Cambridge Institute of Therapeutic Immunology and Infectious Diseases, Department of Medicine, University of Cambridge, Cambridge CB2 0AW, UK.ORCID 0000-0002-8232-4601
Hiran A PragMRC Mitochondrial Biology Unit, University of Cambridge, Cambridge CB2 0XY, UK.ORCID 0000-0002-4753-8567
Michael P MurphyMolecular Immunity Unit, Cambridge Institute of Therapeutic Immunology and Infectious Diseases, Department of Medicine, University of Cambridge, Cambridge CB2 0AW, UK.ORCID 0000-0003-1115-9618
Lalita RamakrishnanMolecular Immunity Unit, Cambridge Institute of Therapeutic Immunology and Infectious Diseases, Department of Medicine, University of Cambridge, Cambridge CB2 0AW, UK.ORCID 0000-0003-0692-5533
University of Cambridge · GBMRC Laboratory of Molecular Biology · GB

Funding

Host-Responses to Mycobacterium Infection in ZebrafishR37AI054503 · NIAID · UNIVERSITY OF WASHINGTON · PI RAMAKRISHNAN, LALITA · 2012 to 2021
$3.1M
Medical Research Council MC_U105663142NIAID NIH HHS R37 AI054503Wellcome Trust 103950Wellcome Trust 110158/Z/15/ZWellcome Trust 110159
6 · The paper itself

Abstract

Tumor necrosis factor (TNF) is a critical host resistance factor against tuberculosis. However, excess TNF produces susceptibility by increasing mitochondrial reactive oxygen species (mROS), which initiate a signaling cascade to cause pathogenic necrosis of mycobacterium-infected macrophages. In zebrafish, we identified the mechanism of TNF-induced mROS in tuberculosis. Excess TNF in mycobacterium-infected macrophages elevates mROS production by reverse electron transport (RET) through complex I. TNF-activated cellular glutamine uptake leads to an increased concentration of succinate, a Krebs cycle intermediate. Oxidation of this elevated succinate by complex II drives RET, thereby generating the mROS superoxide at complex I. The complex I inhibitor metformin, a widely used antidiabetic drug, prevents TNF-induced mROS and necrosis of

Indexed as

Electron Transport Complex IMacrophagesMetforminMycobacterium tuberculosisReactive Oxygen SpeciesTuberculosisTumor Necrosis Factor-alphaAnimalsCitric Acid CycleElectron TransportHumansNecrosisSuccinic AcidZebrafishElectron Transport Complex IMetforminReactive Oxygen SpeciesSuccinic AcidTumor Necrosis Factor-alpha

Identifiers

PMID35737799
PMCPMC7612974
OpenAlexW4283321377

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.