Evidence map›Paper›PMID 30046112›Full record

ArticleNature2018

New mitochondrial DNA synthesis enables NLRP3 inflammasome activation.

Zhenyu Zhong, Shuang Liang, Elsa Sanchez-Lopez, Feng He, Shabnam Shalapour, Xue-Jia Lin, Jerry Wong, Siyuan Ding, Ekihiro Seki, Bernd Schnabl and 4 more

Registry-linked trialAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06261723 (Effect of Non-chirurgical Periodontal Treatment on the Innate and Adaptive Immunity From a Gender Perspective), which is not on this map. Cited by 728 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
728citing papers in PubMed, 1 pooled it
34.2field-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.

NCT06261723 completednot on this mapstarted 2024, after this paper: background citation

Effect of Non-chirurgical Periodontal Treatment on the Innate and Adaptive Immunity From a Gender Perspective: Potential Therapeutic Implications of microRNAs

Typeobservational_patient_registrySponsorMilagros Rocha BarajasRan2024 to 2025Enrolled100ConditionsPeriodontal DiseasesArmsnon-chirurgical periodontal treatment
3 · Its place in the literature

Who cites it

728 citing papers in PubMed, 1 synthesis or guideline pooled it, 1,117 citations in OpenAlex.

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668 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 4 institutions in 2 countries.

Zhenyu ZhongLaboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California San Diego, La Jolla, CA, USA.
Shuang LiangDepartment of Medicine, School of Medicine, University of California San Diego, La Jolla, CA, USA.
Elsa Sanchez-LopezLaboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California San Diego, La Jolla, CA, USA.
Feng HeLaboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California San Diego, La Jolla, CA, USA.
Shabnam ShalapourLaboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California San Diego, La Jolla, CA, USA.
Xue-Jia LinLaboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California San Diego, La Jolla, CA, USA.
Jerry WongLaboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California San Diego, La Jolla, CA, USA.
Siyuan DingDepartment of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
Ekihiro SekiDepartment of Medicine, Division of Gastroenterology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Bernd SchnablDepartment of Medicine, School of Medicine, University of California San Diego, La Jolla, CA, USA.
Andrea L HevenerDepartment of Medicine, Division of Endocrinology, Diabetes and Hypertension, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.
Harry B GreenbergDepartment of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
Tatiana KisselevaDepartment of Surgery, School of Medicine, University of California San Diego, La Jolla, CA, USA.
Michael KarinLaboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California San Diego, La Jolla, CA, USA. karinoffice@ucsd.edu.
University of California, San Diego · USStanford University · USCedars-Sinai Medical Center · USUniversity of California, Los Angeles · US

Funding

Yeast Genetics and Stress Response Genes-BiomedicalP42ES010337 · NIEHS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI TUKEY, ROBERT H · 2000 to 2022
$69.8M
Transgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI PETER J TONTONOZ · 2003 to 2026
$40.4M
Tumor Assessment CoreP01CA128814 · NCI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI SMITH, JEFFREY W · 2009 to 2020
$19.1M
REGULATION OF NFKB AND IKK BY PROINFLAMMATORY STIMULIR01AI043477 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KARIN, MICHAEL · 1998 to 2017
$7.4M
NF-kappaB and Mitochondrial Signals as Positive and Negative Regulators of InflammationR37AI043477 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Michael Karin · 2018 to 2026
$6.0M
Inactivation of Hepatic Stellate Cells During Reversal of Liver FibrosisR01DK099205 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BRENNER, DAVID A., KISSELEVA, TATIANA · 2014 to 2025
$4.8M
LPS binding to TLR4 regulates hepatic stellate cell activation and fibrosisR01DK085252 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI EKIHIRO SEKI · 2011 to 2026
$4.8M
The Role of Portal Fibroblasts in Cholestatic Liver FibrosisR01DK101737 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KISSELEVA, TATIANA · 2014 to 2025
$3.8M
Role of p62/SQSTM1 in obesity-induced liver cancerR01CA211794 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KARIN, MICHAEL, MOSCAT, JORGE · 2017 to 2021
$3.6M
Mechanisms controlling skeletal muscle mitochondrial function and metabolic healthR01DK109724 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI HEVENER, ANDREA L · 2016 to 2020
$2.4M
IKKalpha, autophagy, obesity and injury enhanced pancreatic cancerR01CA163798 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KARIN, MICHAEL · 2012 to 2016
$1.9M
The Role of IL-17 in Alcoholic Liver Disease and CancerU01AA022614 · NIAAA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KARIN, MICHAEL, KISSELEVA, TATIANA · 2014 to 2018
$1.8M
NCI NIH HHS P01 CA128814NCI NIH HHS R01 CA163798NCI NIH HHS R01 CA211794NIAAA NIH HHS R01 AA020172NIAAA NIH HHS U01 AA022614NIAID NIH HHS K99 AI135031NIAID NIH HHS R01 AI043477NIAID NIH HHS R37 AI043477NIDDK NIH HHS P30 DK063491NIDDK NIH HHS R01 DK085252NIDDK NIH HHS R01 DK099205NIDDK NIH HHS R01 DK101737NIDDK NIH HHS R01 DK109724NIDDK NIH HHS R01 DK111866NIEHS NIH HHS P42 ES010337
6 · The paper itself

Abstract

Dysregulated NLRP3 inflammasome activity results in uncontrolled inflammation, which underlies many chronic diseases. Although mitochondrial damage is needed for the assembly and activation of the NLRP3 inflammasome, it is unclear how macrophages are able to respond to structurally diverse inflammasome-activating stimuli. Here we show that the synthesis of mitochondrial DNA (mtDNA), induced after the engagement of Toll-like receptors, is crucial for NLRP3 signalling. Toll-like receptors signal via the MyD88 and TRIF adaptors to trigger IRF1-dependent transcription of CMPK2, a rate-limiting enzyme that supplies deoxyribonucleotides for mtDNA synthesis. CMPK2-dependent mtDNA synthesis is necessary for the production of oxidized mtDNA fragments after exposure to NLRP3 activators. Cytosolic oxidized mtDNA associates with the NLRP3 inflammasome complex and is required for its activation. The dependence on CMPK2 catalytic activity provides opportunities for more effective control of NLRP3 inflammasome-associated diseases.

Indexed as

AnimalsBiocatalysisCytosolDNA, MitochondrialInflammasomesInterferon Regulatory Factor-1LipopolysaccharidesMacrophagesMiceMitochondriaNLR Family, Pyrin Domain-Containing 3 ProteinNucleoside-Phosphate KinaseOxidation-ReductionSignal TransductionToll-Like ReceptorsDNA, MitochondrialInflammasomesInterferon Regulatory Factor-1Irf1 protein, mouseLipopolysaccharidesNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mouseNucleoside-Phosphate KinaseToll-Like Receptors

Identifiers

PMID30046112
PMCPMC6329306
OpenAlexW2884912010

What OpenQuestion holds

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Read underepoch 390

Registered trials

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.