Evidence map›Paper›PMID 41345081›Full record

ArticleNature communications2025

Cytochrome c oxidase dependent respiration is essential for T cell activation, proliferation and memory formation.

Tatiana N Tarasenko, Emily Warren, Bharati Singh, Amanda Fuchs, Jose Marin, Marten Szibor, Christopher King, Peter J McGuire

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Tatiana N TarasenkoMetabolism, Infection, and Immunity Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Emily WarrenMetabolism, Infection, and Immunity Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-3561-3478
Bharati SinghMetabolism, Infection, and Immunity Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Amanda FuchsMetabolism, Infection, and Immunity Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-7085-0727
Jose MarinMetabolism, Infection, and Immunity Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0000-0001-8820-7820
Marten SziborFaculty of Medicine and Health Technology, Tampere University, Tampere, Finland.ORCID http://orcid.org/0000-0003-4029-160X
Christopher KingDivision of Veterinary Recourses, National Institutes of Health, Bethesda, MD, USA.ORCID http://orcid.org/0009-0005-9882-3658
Peter J McGuireMetabolism, Infection, and Immunity Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA. peter.mcguire@nih.gov.ORCID http://orcid.org/0000-0001-5601-3044

Funding

Metabolism, infection and immunity in inborn errors of mitochondrial metabolismZIAHG200381 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI MCGUIRE, PETER · 2012 to 2025
$21.7M
Intramural NIH HHS ZIA HG200381U.S. Department of Health & Human Services | National Institutes of Health (NIH) ZIA HG200381-12
6 · The paper itself

Abstract

T cell activation requires extensive metabolic reprogramming, but the specific requirement for mitochondrial respiration (MR) remains unresolved. While most studies have focused on aerobic glycolysis as the primary driver of proliferation and effector function, the role of MR has not been completely defined. To isolate MR from proton pumping by cytochrome c oxidase (COX), we expressed the non-proton-pumping alternative oxidase (AOX) in activated COX-deficient T cells. AOX restored electron flow, membrane potential, and mitochondrial ATP production, ultimately rescuing proliferation, effector and memory differentiation, and antiviral immunity. These improvements required upstream electron input, particularly from Complex I, with Complex II and DHODH contributing more modestly. Despite restored MR, glycolysis remained elevated, likely due to altered redox signaling. These findings demonstrate that MR, normally mediated by COX, is necessary and can be sufficient to support T cell activation and function, independent of proton translocation, provided upstream electron input is maintained.

Indexed as

Electron Transport Complex IVImmunologic MemoryLymphocyte ActivationT-LymphocytesAdenosine TriphosphateAlternative OxidaseAnimalsCell ProliferationCell RespirationGlycolysisMiceMice, Inbred C57BLMitochondriaMitochondrial ProteinsOxidoreductasesPlant ProteinsAdenosine TriphosphateAlternative OxidaseElectron Transport Complex IVMitochondrial ProteinsOxidoreductasesPlant Proteins

Identifiers

PMID41345081
PMCPMC12678437

What OpenQuestion holds

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LicenceCC BY
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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.