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TRP14 is the rate-limiting enzyme for intracellular cystine reduction and regulates proteome cysteinylation.
Martí-Andrés, Pablo; Finamor, Isabela; Torres-Cuevas, Isabel; Pérez, Salvador; Rius-Pérez, Sergio; Colino-Lage, Hildegard; Guerrero-Gómez, David; Morato, Esperanza; Marina, Anabel; Michalska, Patrycja; León, Rafael; Cheng, Qing; Jurányi, Eszter Petra; Borbényi-Galambos, Klaudia; Millán, Iván; Nagy, Péter; Miranda-Vizuete, Antonio; Schmidt, Edward E; Martínez-Ruiz, Antonio; Arnér, Elias Sj; Sastre, Juan.
Afiliación
  • Martí-Andrés P; Department of Physiology, Faculty of Pharmacy, University of Valencia, Burjassot, Valencia, Spain.
  • Finamor I; Division of Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE 171 77, Stockholm, Sweden.
  • Torres-Cuevas I; Department of Physiology, Faculty of Pharmacy, University of Valencia, Burjassot, Valencia, Spain.
  • Pérez S; Department of Physiology and Pharmacology, Federal University of Santa Maria, Santa Maria, Rio Grande do Sul, Brazil.
  • Rius-Pérez S; Department of Physiology, Faculty of Pharmacy, University of Valencia, Burjassot, Valencia, Spain.
  • Colino-Lage H; Department of Physiology, Faculty of Pharmacy, University of Valencia, Burjassot, Valencia, Spain.
  • Guerrero-Gómez D; Department of Physiology, Faculty of Pharmacy, University of Valencia, Burjassot, Valencia, Spain.
  • Morato E; Redox Homeostasis Group, Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain.
  • Marina A; Redox Homeostasis Group, Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain.
  • Michalska P; Centro de Biología Molecular "Severo Ochoa" (CBMSO), CSIC-UAM, Madrid, Spain.
  • León R; Centro de Biología Molecular "Severo Ochoa" (CBMSO), CSIC-UAM, Madrid, Spain.
  • Cheng Q; Unidad de Técnicas Bioanalíticas (BAT), Instituto de Investigación de Ciencias de la Alimentación (CIAL), CSIC-UAM, Madrid, Spain.
  • Jurányi EP; Department of Chemistry, Molecular Sciences Research Hub, Imperial College London, London, UK.
  • Borbényi-Galambos K; Institute of Medical Chemistry, CSIC, Madrid, Spain.
  • Millán I; Division of Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE 171 77, Stockholm, Sweden.
  • Nagy P; Department of Molecular Immunology and Toxicology and the National Tumor Biology Laboratory, National Institute of Oncology, Budapest, Hungary.
  • Miranda-Vizuete A; Molecular Medicine Division, Semmelweis University Doctoral College, Budapest, Hungary.
  • Schmidt EE; Department of Molecular Immunology and Toxicology and the National Tumor Biology Laboratory, National Institute of Oncology, Budapest, Hungary.
  • Martínez-Ruiz A; Kálmán Laki Doctoral School, University of Debrecen, Debrecen, Hungary.
  • Arnér ES; Instituto Cavanilles de Biodiversidad y Biología Evolutiva, Universidad de Valencia, Paterna, Valencia, Spain.
  • Sastre J; Department of Molecular Immunology and Toxicology and the National Tumor Biology Laboratory, National Institute of Oncology, Budapest, Hungary.
EMBO J ; 43(13): 2789-2812, 2024 Jul.
Article en En | MEDLINE | ID: mdl-38811853
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Oxidación-Reducción / Tiorredoxinas / Caenorhabditis elegans / Ratones Noqueados / Proteoma / Cisteína / Cistina Límite: Animals / Humans Idioma: En Revista: EMBO J Año: 2024 Tipo del documento: Article País de afiliación: España Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Oxidación-Reducción / Tiorredoxinas / Caenorhabditis elegans / Ratones Noqueados / Proteoma / Cisteína / Cistina Límite: Animals / Humans Idioma: En Revista: EMBO J Año: 2024 Tipo del documento: Article País de afiliación: España Pais de publicación: Reino Unido