Evidence map›Paper›PMID 37607904›Full record

ArticleNature communications2023

Pyruvate dehydrogenase operates as an intramolecular nitroxyl generator during macrophage metabolic reprogramming.

Erika M Palmieri, Ronald Holewinski, Christopher L McGinity, Ciro L Pierri, Nunziata Maio, Jonathan M Weiss, Vincenzo Tragni, Katrina M Miranda, Tracey A Rouault, Thorkell Andresson and 2 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
10.5field-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

33 citing papers in PubMed, 44 citations in OpenAlex.

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  11. Effect of PKM2 onFrontiers in cellular and infection microbiology · 2026
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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

12 authors at 5 institutions in 2 countries.

Erika M PalmieriCancer Innovation Laboratory, NCI-Frederick, Frederick, MD, 21702, USA.ORCID http://orcid.org/0000-0002-4237-5324
Ronald HolewinskiProtein Characterization Laboratory, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, 21702, USA.
Christopher L McGinityCancer Innovation Laboratory, NCI-Frederick, Frederick, MD, 21702, USA.
Ciro L PierriLaboratory of Biochemistry, Molecular and Structural Biology, Department of Pharmacy-Pharmaceutical Sciences, University of Bari, Via E. Orabona, 4, Bari, 70125, Italy.
Nunziata MaioMolecular Medicine Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, 9000 Rockville Pike, Bethesda, MD, 20892, USA.ORCID http://orcid.org/0000-0002-6225-6058
Jonathan M WeissCancer Innovation Laboratory, NCI-Frederick, Frederick, MD, 21702, USA.ORCID http://orcid.org/0000-0002-4467-5611
Vincenzo TragniLaboratory of Biochemistry, Molecular and Structural Biology, Department of Pharmacy-Pharmaceutical Sciences, University of Bari, Via E. Orabona, 4, Bari, 70125, Italy.
Katrina M MirandaDepartment of Chemistry and Biochemistry, University of Arizona, Tucson, AZ, 85721, USA.ORCID http://orcid.org/0000-0002-9175-5091
Tracey A RouaultMolecular Medicine Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, 9000 Rockville Pike, Bethesda, MD, 20892, USA.
Thorkell AndressonProtein Characterization Laboratory, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, 21702, USA.
David A WinkCancer Innovation Laboratory, NCI-Frederick, Frederick, MD, 21702, USA.
Daniel W McVicarCancer Innovation Laboratory, NCI-Frederick, Frederick, MD, 21702, USA. mcvicard@mail.nih.gov.ORCID http://orcid.org/0000-0002-1112-5111
Frederick National Laboratory for Cancer Research · USEunice Kennedy Shriver National Institute of Child Health and Human Development · USLeidos (United States) · USUniversity of Bari Aldo Moro · ITUniversity of Arizona · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

M1 macrophages enter a glycolytic state when endogenous nitric oxide (NO) reprograms mitochondrial metabolism by limiting aconitase 2 and pyruvate dehydrogenase (PDH) activity. Here, we provide evidence that NO targets the PDH complex by using lipoate to generate nitroxyl (HNO). PDH E2-associated lipoate is modified in NO-rich macrophages while the PDH E3 enzyme, also known as dihydrolipoamide dehydrogenase (DLD), is irreversibly inhibited. Mechanistically, we show that lipoate facilitates NO-mediated production of HNO, which interacts with thiols forming irreversible modifications including sulfinamide. In addition, we reveal a macrophage signature of proteins with reduction-resistant modifications, including in DLD, and identify potential HNO targets. Consistently, DLD enzyme is modified in an HNO-dependent manner at Cys

Indexed as

Nitric OxideNitrogen OxidesMacrophagesOxidoreductasesPyruvate Dehydrogenase ComplexPyruvatesNitric OxideNitrogen OxidesnitroxylOxidoreductasesPyruvate Dehydrogenase ComplexPyruvates

Identifiers

PMID37607904
PMCPMC10444860
OpenAlexW4386047576

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.