Evidence map›Paper›PMID 40033006›Full record

ArticleNature metabolism2025

Regulation of mammalian cellular metabolism by endogenous cyanide production.

Karim Zuhra, Maria Petrosino, Lucia Janickova, Jovan Petric, Kelly Ascenção, Thibaut Vignane, Moustafa Khalaf, Thilo M Philipp, Stella Ravani, Abhishek Anand and 18 more

Abstract read
In one paragraph

Article in Nature metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed, 1 pooled it
–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

28 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Catechol-Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  3. Article
  4. Article
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  12. Article
  13. Article
  14. Review
  15. Article
  16. Cystathionine γ-lyase is a major regulator of cognitive function through neurotrophin signaling and neurogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  17. Review
  18. Article
  19. Review
  20. Black gas, bright future: HNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025
    Review
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

28 authors.

Karim Zuhra *Section of Pharmacology, Department of Oncology, Microbiology and Immunology, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland.ORCID http://orcid.org/0000-0003-0186-1817
Maria Petrosino *Section of Pharmacology, Department of Oncology, Microbiology and Immunology, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland.ORCID http://orcid.org/0000-0001-7875-5954
Lucia JanickovaSection of Pharmacology, Department of Oncology, Microbiology and Immunology, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland.ORCID http://orcid.org/0000-0001-5429-0363
Jovan PetricLeibniz Institute for Analytical Sciences, Dortmund, Germany.ORCID http://orcid.org/0009-0001-2855-0165
Kelly AscençãoSection of Pharmacology, Department of Oncology, Microbiology and Immunology, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland.ORCID http://orcid.org/0000-0001-6693-6897
Thibaut VignaneLeibniz Institute for Analytical Sciences, Dortmund, Germany.ORCID http://orcid.org/0000-0002-3377-3187
Moustafa KhalafDepartment of Chemistry and Biochemistry, South Dakota State University, Brookings, SD, USA.
Thilo M PhilippSection of Pharmacology, Department of Oncology, Microbiology and Immunology, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland.ORCID http://orcid.org/0000-0002-4730-4218
Stella RavaniClinical, Experimental Surgery and Translational Research Center, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.ORCID http://orcid.org/0009-0009-0145-0525
Abhishek AnandSection of Pharmacology, Department of Oncology, Microbiology and Immunology, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland.ORCID http://orcid.org/0000-0001-8055-6970
Vanessa MartinsSection of Pharmacology, Department of Oncology, Microbiology and Immunology, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland.
Sidneia SantosSection of Pharmacology, Department of Oncology, Microbiology and Immunology, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland.ORCID http://orcid.org/0000-0002-6807-9881
Serkan ErdemirSelcuk University, Science Faculty, Department of Chemistry, Konya, Turkey.
Sait MalkonduGiresun University, Faculty of Engineering, Department of Environmental Engineering, Giresun, Turkey.
Barbara SitekJagiellonian Centre for Experimental Therapeutics, Jagiellonian University, Krakow, Poland.
Taha KelestemurDepartment of Anesthesiology, Columbia University, New York, NY, USA.ORCID http://orcid.org/0000-0003-3616-1204
Anna Kieronska-RudekSection of Pharmacology, Department of Oncology, Microbiology and Immunology, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland.ORCID http://orcid.org/0000-0002-5447-0812
Tomas MajtanSection of Pharmacology, Department of Oncology, Microbiology and Immunology, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland.ORCID http://orcid.org/0000-0002-2751-2124
Luis FilgueiraSection of Anatomy, Department of Oncology, Microbiology and Immunology, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland.
Darko MaricDepartment of Endocrinology, Metabolism and Cardiovascular System, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland.
Stefan ChlopickiJagiellonian Centre for Experimental Therapeutics, Jagiellonian University, Krakow, Poland.ORCID http://orcid.org/0000-0002-2878-3858
David HoogewijsDepartment of Endocrinology, Metabolism and Cardiovascular System, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland.ORCID http://orcid.org/0000-0001-5547-6004
György HaskóDepartment of Anesthesiology, Columbia University, New York, NY, USA.
Andreas PapapetropoulosClinical, Experimental Surgery and Translational Research Center, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.ORCID http://orcid.org/0000-0002-4253-5930
Brian A LogueDepartment of Chemistry and Biochemistry, South Dakota State University, Brookings, SD, USA.ORCID http://orcid.org/0000-0002-2400-9339
Gerry R BossDepartment of Medicine, University of California, San Diego, San Diego, CA, USA.
Milos R FilipovicLeibniz Institute for Analytical Sciences, Dortmund, Germany. milos.filipovic@glasgow.ac.uk.ORCID http://orcid.org/0000-0003-0060-0041
Csaba SzaboSection of Pharmacology, Department of Oncology, Microbiology and Immunology, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland. csaba.szabo@unifr.ch.ORCID http://orcid.org/0000-0003-3110-4235

Funding

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation) #310030L_204371
6 · The paper itself

Abstract

Small, gaseous molecules such as nitric oxide, carbon monoxide and hydrogen sulfide are produced as signalling molecules in mammalian cells. Here, we show that low concentrations of cyanide are generated endogenously in various mammalian tissues and cells. We detect cyanide in several cellular compartments of human cells and in various tissues and the blood of mice. Cyanide production is stimulated by glycine, occurs at the low pH of lysosomes and requires peroxidase activity. When generated at a specific rate, cyanide exerts stimulatory effects on mitochondrial bioenergetics, cell metabolism and cell proliferation, but impairs cellular bioenergetics at high concentrations. Cyanide can modify cysteine residues via protein S-cyanylation, which is detectable basally in cells and mice, and increases in response to glycine. Low-dose cyanide supplementation exhibits cytoprotective effects in hypoxia and reoxygenation models in vitro and in vivo. Conversely, pathologically elevated cyanide production in nonketotic hyperglycinaemia is detrimental to cells. Our findings indicate that cyanide should be considered part of the same group of endogenous mammalian regulatory gasotransmitters as nitric oxide, carbon monoxide and hydrogen sulfide.

Indexed as

CyanidesAnimalsEnergy MetabolismGlycineHumansMiceMitochondriaCyanidesGlycine

Identifiers

PMID40033006
PMCPMC11946912

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.