Evidence map›Paper›PMID 35298263›Full record

ArticleScience (New York, N.Y.)2022

Copper induces cell death by targeting lipoylated TCA cycle proteins.

Peter Tsvetkov, Shannon Coy, Boryana Petrova, Margaret Dreishpoon, Ana Verma, Mai Abdusamad, Jordan Rossen, Lena Joesch-Cohen, Ranad Humeidi, Ryan D Spangler and 8 more

Erratum issuedOpen access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Science (New York, N.Y.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 2,605 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
2,605citing papers in PubMed, 1 pooled it
482.9field-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

2,605 citing papers in PubMed, 1 synthesis or guideline pooled it, 4,375 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Article
  6. Review
  7. CuBioactive materials · 2026
    Article
  8. Article
  9. Article
  10. Genes, fuel, and fate in lung cancer.Biochemical Society transactions · 2026
    Review
  11. Review
  12. Cuproptosis and the bioinorganic basis of copper-induced cell death.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2026
    Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. Review
  18. Review
  19. Unveiling the pathogenesis and therapeutic strategies of Alzheimer's disease through cuproptosis.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026
    Review
  20. Article

2,545 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 5 institutions in 1 country.

Peter TsvetkovBroad Institute of Harvard and MIT, Cambridge, MA, USA.ORCID 0000-0002-7577-2342
Shannon CoyLaboratory of Systems Pharmacology, Department of Systems Biology, Boston, MA, USA.ORCID 0000-0003-0033-9031
Boryana PetrovaHarvard Medical School, Boston, MA, USA.ORCID 0000-0001-9996-9353
Margaret DreishpoonBroad Institute of Harvard and MIT, Cambridge, MA, USA.ORCID 0000-0002-4432-6673
Ana VermaLaboratory of Systems Pharmacology, Department of Systems Biology, Boston, MA, USA.ORCID 0000-0001-9057-171X
Mai AbdusamadBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Jordan RossenBroad Institute of Harvard and MIT, Cambridge, MA, USA.ORCID 0000-0002-1661-6358
Lena Joesch-CohenBroad Institute of Harvard and MIT, Cambridge, MA, USA.ORCID 0000-0002-9129-6809
Ranad HumeidiBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Ryan D SpanglerBroad Institute of Harvard and MIT, Cambridge, MA, USA.
John K EatonBroad Institute of Harvard and MIT, Cambridge, MA, USA.ORCID 0000-0003-4633-5546
Evgeni FrenkelWhitehead Institute and Massachusetts Institute of Technology, Cambridge, MA, USA.
Mustafa KocakBroad Institute of Harvard and MIT, Cambridge, MA, USA.
Steven M CorselloBroad Institute of Harvard and MIT, Cambridge, MA, USA.ORCID 0000-0002-9929-3709
Svetlana LutsenkoDepartment of Physiology, Johns Hopkins Medical Institutes, Baltimore, MD, USA.ORCID 0000-0001-5275-2587
Naama KanarekBroad Institute of Harvard and MIT, Cambridge, MA, USA.ORCID 0000-0002-2068-3908
Sandro SantagataLaboratory of Systems Pharmacology, Department of Systems Biology, Boston, MA, USA.ORCID 0000-0002-7528-9668
Todd R GolubBroad Institute of Harvard and MIT, Cambridge, MA, USA.ORCID 0000-0003-0113-2403
Broad Institute · USBrigham and Women's Hospital · USBoston Children's Hospital · USJohns Hopkins University · USWhitehead Institute for Biomedical Research · US

Funding

TRAINING GRANT IN GENETICST32GM007748 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI Anne O'Donnell-Luria, Louise Wilkins-Haug · 1985 to 2026
$12.0M
Systems Pharmacology of Therapeutic and Adverse Responses to ImmuneCheckpoint and Small Molecule DrugsU54CA225088 · NCI · HARVARD MEDICAL SCHOOL · PI SHARPE, ARLENE H. · 2018 to 2022
$10.8M
Making cancer precision medicine real: bottlenecks and opportunitiesR35CA242457 · NCI · BROAD INSTITUTE, INC. · PI GOLUB, TODD R. · 2019 to 2025
$6.9M
Investigating the HSF1 Cancer NetworkR01CA194005 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI SANTAGATA, SANDRO · 2016 to 2020
$2.0M
Targeting casein kinase 1-alpha for cancer therapyK08CA230220 · NCI · STANFORD UNIVERSITY · PI CORSELLO, STEVEN MUNTEAN · 2018 to 2022
$1.0M
NCI NIH HHS K08 CA230220NCI NIH HHS R01 CA194005NCI NIH HHS R35 CA242457NCI NIH HHS U54 CA225088NIGMS NIH HHS T32 GM007748
6 · The paper itself

Abstract

Copper is an essential cofactor for all organisms, and yet it becomes toxic if concentrations exceed a threshold maintained by evolutionarily conserved homeostatic mechanisms. How excess copper induces cell death, however, is unknown. Here, we show in human cells that copper-dependent, regulated cell death is distinct from known death mechanisms and is dependent on mitochondrial respiration. We show that copper-dependent death occurs by means of direct binding of copper to lipoylated components of the tricarboxylic acid (TCA) cycle. This results in lipoylated protein aggregation and subsequent iron-sulfur cluster protein loss, which leads to proteotoxic stress and ultimately cell death. These findings may explain the need for ancient copper homeostatic mechanisms.

Indexed as

Citric Acid CycleRegulated Cell DeathAnimalsCell RespirationCopperDihydrolipoyllysine-Residue AcetyltransferaseHepatolenticular DegenerationHomeostasisHumansHydrazinesIonophoresIron-Sulfur ProteinsLipoylationMetabolic Networks and PathwaysMiceMitochondriaCopperDihydrolipoyllysine-Residue AcetyltransferaseelesclomolHydrazinesIonophoresIron-Sulfur Proteins

Identifiers

PMID35298263
PMCPMC9273333
OpenAlexW4221115671

What Socratic holds

Textmetadata
LicenceTDM
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.