Evidence map›Paper›PMID 39753784›Full record

ArticleEMBO reports2025

Pro-inflammatory macrophage activation does not require inhibition of oxidative phosphorylation.

Andréa B Ball, Anthony E Jones, Kaitlyn B Nguyễn, Amy Rios, Nico Marx, Wei Yuan Hsieh, Krista Yang, Brandon R Desousa, Kristen K O Kim, Michaela Veliova and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in EMBO reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
–field-weighted citation impact
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

13 citing papers in PubMed.

  1. Metabolomics ofbioRxiv : the preprint server for biology · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors.

Andréa B BallDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0002-8214-7190
Anthony E JonesDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0003-2058-6021
Kaitlyn B NguyễnDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
Amy RiosDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
Nico MarxInstitute of Integrative Cell Biology and Physiology, Bioenergetics and Mitochondrial Dynamics Section, University of Münster, Schloßplatz 5, D-49078, Münster, Germany.ORCID http://orcid.org/0000-0003-3745-261X
Wei Yuan HsiehDepartment of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
Krista YangDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
Brandon R DesousaDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0003-3765-3809
Kristen K O KimDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0001-8376-3131
Michaela VeliovaDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
Zena Marie Del MundoDepartment of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0002-4997-379X
Orian S ShirihaiDepartment of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0001-8466-3431
Cristiane BenincáDepartment of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0001-7933-860X
Linsey StilesDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
Steven J BensingerDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0002-9657-4206
Ajit S DivakaruniDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA. adivakaruni@mednet.ucla.edu.ORCID http://orcid.org/0000-0002-2528-9651

Funding

Virology CoreP30AI028697 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BALDWIN, GAYLE COCITA · 1991 to 2018
$39.9M
Understanding the Influence of Lipid Homeostasis on T cell FunctionP01HL146358 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI YOUNG, STEPHEN G. · 2019 to 2023
$11.7M
TUMOR CELL SURFACES AND CHROMOSOMEST32CA009056 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Gay M Crooks, David A. Nathanson · 1985 to 2026
$10.5M
Restorative practice in repairing harm and promoting safe and inclusive practices in the laboratory.T32GM136547 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Adrian Erlebacher, Anita Sil · 2020 to 2026
$4.5M
Understanding How Metabolic Cofactors Control Cell Function and FateR35GM138003 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Ajit Divakaruni · 2020 to 2026
$2.8M
Chemistry Biology Interface Training ProgramT32GM136614 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Patrick G. Harran · 2020 to 2026
$2.8M
Investigating the impact of a fatty acid-cRel inflammatory circuit in atherosclerosisR01HL157710 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BENSINGER, STEVEN J · 2021 to 2024
$2.3M
Agilent Technologies (Agilent) 4814HHS | National Institutes of Health (NIH) P01HL146358HHS | National Institutes of Health (NIH) R01HL157710HHS | National Institutes of Health (NIH) R35GM138003HHS | National Institutes of Health (NIH) T32CA009056HHS | National Institutes of Health (NIH) T32GM136614NCI NIH HHS T32 CA009056NHLBI NIH HHS P01 HL146358NHLBI NIH HHS R01 HL157710NIAID NIH HHS P30 AI028697NIGMS NIH HHS R35 GM138003NIGMS NIH HHS T32 GM136547NIGMS NIH HHS T32 GM136614W. M. Keck Foundation (WMKF) 995337
6 · The paper itself

Abstract

Pro-inflammatory macrophage activation is a hallmark example of how mitochondria serve as signaling organelles. Oxidative phosphorylation sharply decreases upon classical macrophage activation, as mitochondria are thought to shift from ATP production towards accumulating signals that amplify effector function. However, evidence is conflicting regarding whether this collapse in respiration is essential or dispensable. Here we systematically examine this question and show that reduced oxidative phosphorylation is not required for pro-inflammatory macrophage activation. Different pro-inflammatory stimuli elicit varying effects on bioenergetic parameters, and pharmacologic and genetic models of electron transport chain inhibition show no causative link between respiration and macrophage activation. Furthermore, the signaling metabolites succinate and itaconate can accumulate independently of characteristic breaks in the TCA cycle in mouse and human macrophages, and peritoneal macrophages can be activated in vivo without inhibition of oxidative phosphorylation. The results indicate there is plasticity in the metabolic phenotypes that can support pro-inflammatory macrophage activation.

Indexed as

InflammationMacrophage ActivationMacrophagesOxidative PhosphorylationAnimalsCitric Acid CycleHumansMacrophages, PeritonealMiceMice, Inbred C57BLMitochondriaSignal TransductionSuccinatesSuccinic Aciditaconic acidSuccinatesSuccinic AcidImmunometabolismItaconateMacrophage PolarizationMitochondrial SignalingOxidative Phosphorylation

Identifiers

PMID39753784
PMCPMC11850891

What Socratic 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 Socratic graph.