‘This indicates that cysteine metabolism plays a relevant role in diseases and is a new therapeutic strategy in inflammatory processes,’ explains Juan Sastre, Full-time university professor in the Department of Physiology at the Universitat de València and director of the research, which is the result of project PID2019-108615RB-I00 of the State Research Agency of the Ministry.

The intracellular reduction of cystine to cysteine is essential to provide this amino acid (cysteine) to cells, which is necessary for both protein synthesis and the training of glutathione, the most important intracellular antioxidant that protects against intracellular oxidative damage. ‘When TRP14 is deficient, the trans-sulphuration pathway is induced to synthesise cysteine from methionine, as an adaptive mechanism to ensure the availability of cysteine to cells,’ explains Juan Sastre.

These results have been published by UV researchers in collaboration with the Karolinska Institute in Stockholm (Sweden), the Institute of Biomedicine of Seville (IBIS), the Princess of Madrid Health Research Institute (IIS_IP), the Institute of Medical Chemistry of the Spanish National Research Council (CSIC) in Madrid, and the Montana State University in the United States.

Juan Sastre says that the next step in this research is to study the possible therapeutic application of TRP14 modulation in both inflammatory and tumour processes.

Scientific article reference:

Martí-Andrés P, Finamor I, Torres-Cuevas I, Pérez S, Rius-Pérez S, Colino-Lage H, Guerrero-Gómez D, Morato E, Marina A, Michalska P, León R, Cheng Q, Jurányi EP, Borbényi-Galambos K, Millán I, Nagy P, Miranda-Vizuete A, Schmidt EE, Martínez-Ruiz A, Arnér ES, Sastre J. TRP14 is the rate-limiting enzyme for intracellular cystine reduction and regulates proteome cysteinylation. EMBO J. 2024; 43(13):2789-2812. doi: 10.1038/s44318-024-00117-1