ArticleThe EMBO journal2024
TRP14 is the rate-limiting enzyme for intracellular cystine reduction and regulates proteome cysteinylation.
Abstract read
In one paragraph
Article in The EMBO journal, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
–field-weighted citation impact
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.
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.
Who cites it
17 citing papers in PubMed.
- Disulfidptosis: molecular mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Review
- Mechanistic insights into TXNDC17-mediated ferroptosis suppression in glioblastoma progression.Biology direct · 2026Article
- Disulfidptosis and its molecular mechanisms in cancer: mechanisms, regulation, and therapeutic potential.Medical oncology (Northwood, London, England) · 2026Review
- Obesity suppresses neutrophil-dependent itaconate signaling promoting ferroptosis in acute pancreatitis.Redox biology · 2026Article
- Cystine C-S bond cleavage fuels cysteine production under disulfide reductase deficiency.Nature chemical biology · 2026Article
- Cysteine addiction in drug resistant glioblastoma and therapeutic targeting with designer selenium compounds.Neuro-oncology · 2026Article
- Glutamine metabolism and its roles in tumor radiotherapy by regulating DNA damage repair.Frontiers in cell and developmental biology · 2026Review
- PK11007 Covalently Inhibits Thioredoxin Reductase 1 to Induce Oxidative Stress and Autophagy Impairment in NSCLC Cells.Antioxidants (Basel, Switzerland) · 2025Article
- Cysteine Signalling in Plant Pathogen Response.Plant, cell & environment · 2025Article
- The transsulfuration pathway suppresses the embryonic lethal phenotype of glutathione reductase mutants in Caenorhabditis elegans.G3 (Bethesda, Md.) · 2025Article
- Origins of Ultrasensitivity and Complex Signaling Dynamics of Cellular Hydrogen Peroxide and Peroxiredoxin.Antioxidants (Basel, Switzerland) · 2025Article
- Dual Roles of Reducing Systems in Protein Persulfidation and Depersulfidation.Antioxidants (Basel, Switzerland) · 2025Review
- Research progress and potential therapeutic targets of a novel disulfide stress-driven cell death-disulfidptosis in gynecological tumors and other gynecological disorders.American journal of cancer research · 2025Review
- Ferroptosis in central nervous system injuries: molecular mechanisms, diagnostic approaches, and therapeutic strategies.Frontiers in cellular neuroscience · 2025Review
- An Update on Oxidative Stress and Redoxins in Pancreatitis.Cellular and molecular gastroenterology and hepatology · 2025Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors.
Pablo Martí-AndrésDepartment of Physiology, Faculty of Pharmacy, University of Valencia, Burjassot, Valencia, Spain.ORCID https://orcid.org/0000-0003-2112-4857
Isabela FinamorDepartment of Physiology, Faculty of Pharmacy, University of Valencia, Burjassot, Valencia, Spain.
Isabel Torres-CuevasDepartment of Physiology, Faculty of Pharmacy, University of Valencia, Burjassot, Valencia, Spain.ORCID https://orcid.org/0000-0002-8098-1106
Salvador PérezDepartment of Physiology, Faculty of Pharmacy, University of Valencia, Burjassot, Valencia, Spain.ORCID http://orcid.org/0000-0003-0766-1744
Sergio Rius-PérezDepartment of Physiology, Faculty of Pharmacy, University of Valencia, Burjassot, Valencia, Spain.ORCID http://orcid.org/0000-0002-8997-7621
Hildegard Colino-LageRedox Homeostasis Group, Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain.ORCID http://orcid.org/0000-0002-8290-6070
David Guerrero-GómezRedox Homeostasis Group, Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain.ORCID http://orcid.org/0000-0001-9403-6431
Esperanza MoratoCentro de Biología Molecular "Severo Ochoa" (CBMSO), CSIC-UAM, Madrid, Spain.ORCID http://orcid.org/0000-0003-4768-895X
Anabel MarinaCentro de Biología Molecular "Severo Ochoa" (CBMSO), CSIC-UAM, Madrid, Spain.
Patrycja MichalskaDepartment of Chemistry, Molecular Sciences Research Hub, Imperial College London, London, UK.
Rafael LeónInstitute of Medical Chemistry, CSIC, Madrid, Spain.
Qing ChengDivision of Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE 171 77, Stockholm, Sweden.
Eszter Petra JurányiDepartment of Molecular Immunology and Toxicology and the National Tumor Biology Laboratory, National Institute of Oncology, Budapest, Hungary.ORCID http://orcid.org/0000-0002-0563-4876
Klaudia Borbényi-GalambosDepartment of Molecular Immunology and Toxicology and the National Tumor Biology Laboratory, National Institute of Oncology, Budapest, Hungary.
Iván MillánInstituto Cavanilles de Biodiversidad y Biología Evolutiva, Universidad de Valencia, Paterna, Valencia, Spain.
Péter NagyDepartment of Molecular Immunology and Toxicology and the National Tumor Biology Laboratory, National Institute of Oncology, Budapest, Hungary.
Antonio Miranda-VizueteRedox Homeostasis Group, Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain.ORCID http://orcid.org/0000-0002-6856-5396
Edward E SchmidtDepartment of Anatomy and Histology, HUN-REN-UVMB Laboratory of Redox Biology, University of Veterinary Medicine, Budapest, Hungary.ORCID http://orcid.org/0000-0002-9959-4990
Antonio Martínez-RuizUnidad de Investigación, Hospital Universitario Santa Cristina, Instituto de Investigación Sanitaria Princesa (IIS_IP), Madrid, Spain.
Elias Sj ArnérDivision of Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE 171 77, Stockholm, Sweden. elias.arner@ki.se.ORCID http://orcid.org/0000-0002-4807-6114
Juan SastreDepartment of Physiology, Faculty of Pharmacy, University of Valencia, Burjassot, Valencia, Spain. juan.sastre@uv.es.ORCID http://orcid.org/0000-0002-4260-6604
Funding
Enhancing and expanding the CGC Strain CollectionP40OD010440 · OD · UNIVERSITY OF MINNESOTA · PI Aric L Daul, Ann E. Rougvie · 2012 to 2026
$7.5MSouth Carolina COBRE in Oxidants, Redox Balance and Stress SignalingP30GM140964 · NIGMS · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI EBLEN, SCOTT T · 2021 to 2025
$6.4MProject 3 - Pain-induced Sympathoexcitation: Effect of OMMU19AT002023 · NCCIH · UNIVERSITY OF NORTH TEXAS HLTH SCI CTR · PI SMITH, MICHAEL LAMAR · 2004 to 2009
$3.0MImpact of hepatocyte lineage life history dynamics on liver homeostasis in the agR01AG040020 · NIA · MONTANA STATE UNIVERSITY - BOZEMAN · PI GEDEON, TOMAS, SCHMIDT, EDWARD E · 2011 to 2015
$1.5MMetabolic basis of the NADPH-independent disulfide reductase system in mouse liverR01DK123738 · NIDDK · MONTANA STATE UNIVERSITY - BOZEMAN · PI DENICOLA, GINA MARIE, SCHMIDT, EDWARD E · 2020 to 2022
$1.3MMetabolic basis of the NADPH-independent disulfide reductase system in mouse liverR56DK123738 · NIDDK · MONTANA STATE UNIVERSITY - BOZEMAN · PI DENICOLA, GINA MARIE, SCHMIDT, EDWARD E · 2019 to 2019
$464kHepatocyte-targeted somatic-cell genetic complementation in miceR21OD026444 · OD · MONTANA STATE UNIVERSITY - BOZEMAN · PI SCHMIDT, EDWARD E · 2019 to 2020
$396kRedox regulation in the hepatostatR21AG055022 · NIA · MONTANA STATE UNIVERSITY - BOZEMAN · PI ARNER, ELIAS S.J., NAGY, PETER · 2016 to 2017
$382kInitiation, persistence, and progression of hepatocellular carcinomaR21CA152559 · NCI · MONTANA STATE UNIVERSITY - BOZEMAN · PI SCHMIDT, EDWARD E · 2010 to 2011
$310kConserjería de Economía, Conocimiento, Empresas y Universidad, Junta de Andalucía, Spain P20_00229Hungarian Academy of Sciences AT02023-26Hungarian LKH Foundation and Hungarian Magyar Tudományos Akadémia K-22 #143769Hungarian Thematic Excellence Program TKP2021-EGA-44Hungarian Thematic Excellence Programme TKP2021-EGA-44Hungary Ministry of Culture and Innovation 2022-2.1.1-NL-2022-00010HUN-REN Hungarian Research Network 1500207MEC | Agencia Estatal de Investigación (AEI) PGC2018-094276-B-I00MEC | Agencia Estatal de Investigación (AEI) PID2019-108615RB-I00MEC | Agencia Estatal de Investigación (AEI) PID2021-122311NB-I00MEC | Agencia Estatal de Investigación (AEI) PID2021-123481OB-I00MEC | Agencia Estatal de Investigación (AEI) PID2021-124688OB-I00MEC | Agencia Estatal de Investigación (AEI) PRE2019-088198MEC | Agencia Estatal de Investigación (AEI) RED2018-102576-TMEC | Agencia Estatal de Investigación (AEI) RTI2018-094203-B-I00MEC | Instituto de Salud Carlos III (ISCIII) PT17/0019/0018Ministry of Economy and Competitiveness from Spain SAF2015-71208-RNational Tumor Laboratory Project 2022-2.1.1-NL-2022-00010NCCIH NIH HHS U19 AT002023NCI NIH HHS R21 CA152559NIA NIH HHS R01 AG040020NIA NIH HHS R21 AG055022NIDDK NIH HHS R01 DK123738NIDDK NIH HHS R56 DK123738NIGMS NIH HHS P30 GM140964NIH HHS P40 OD010440NIH HHS R21 OD026444Swedish Cancer Society 21 1463 PjSwedish Research Council 2021-02214The Knut and Allice Wallenberg Foundations KAW 2019.0059The National Research. Development and Innovation Office ED_18-1-2019-0025United States National Institutes of Health AG040020United States National Institutes of Health AG055022United States National Institutes of Health DK123738United States National Institutes of Health OD026444United States National Institutes of Health P30GM140964
Abstract
It has remained unknown how cells reduce cystine taken up from the extracellular space, which is a required step for further utilization of cysteine in key processes such as protein or glutathione synthesis. Here, we show that the thioredoxin-related protein of 14 kDa (TRP14, encoded by TXNDC17) is the rate-limiting enzyme for intracellular cystine reduction. When TRP14 is genetically knocked out, cysteine synthesis through the transsulfuration pathway becomes the major source of cysteine in human cells, and knockout of both pathways becomes lethal in C. elegans subjected to proteotoxic stress. TRP14 can also reduce cysteinyl moieties on proteins, rescuing their activities as here shown with cysteinylated peroxiredoxin 2. Txndc17 knockout mice were, surprisingly, protected in an acute pancreatitis model, concomitant with activation of Nrf2-driven antioxidant pathways and upregulation of transsulfuration. We conclude that TRP14 is the evolutionarily conserved enzyme principally responsible for intracellular cystine reduction in C. elegans, mice, and humans.
Indexed as
Caenorhabditis elegansCysteineCystineMice, KnockoutOxidation-ReductionProteomeThioredoxinsAnimalsCaenorhabditis elegans ProteinsHumansMicePeroxiredoxinsCaenorhabditis elegans ProteinsCysteineCystinePeroxiredoxinsProteomeThioredoxinsTXNDC17 protein, humanAcute PancreatitisCysteine HomeostasisProtein CysteinylationProteotoxic StressTranssulfuration
Identifiers
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.