132790 20260217205449.0 doi 10.1016/j.redox.2023.103001 sideral 137761 ART-2024-137761 eng Curtabbi, Andrea Regulation of respiratory complex I assembly by FMN cofactor targeting 2024 Access copy available to the general public Unrestricted Respiratory complex I plays a crucial role in the mitochondrial electron transport chain and shows promise as a therapeutic target for various human diseases. While most studies focus on inhibiting complex I at the Q-site, little is known about inhibitors targeting other sites within the complex. In this study, we demonstrate that diphenyleneiodonium (DPI), a N-site inhibitor, uniquely affects the stability of complex I by reacting with its flavin cofactor FMN. Treatment with DPI blocks the final stage of complex I assembly, leading to the complete and reversible degradation of complex I in different cellular models. Growing cells in medium lacking the FMN precursor riboflavin or knocking out the mitochondrial flavin carrier gene SLC25A32 results in a similar complex I degradation. Overall, our findings establish a direct connection between mitochondrial flavin homeostasis and complex I stability and assembly, paving the way for novel pharmacological strategies to regulate respiratory complex I. info:eu-repo/grantAgreement/ES/DGA/E35-23R info:eu-repo/grantAgreement/ES/MICINN/PID2021-127988OB-I00 info:eu-repo/grantAgreement/ES/MICINN/PID2022-136369NB-I00 info:eu-repo/grantAgreement/ES/MICINN/TED2021-131611B-I00 info:eu-repo/semantics/openAccess by-nc-nd https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es 11.9 2024 BIOCHEMISTRY & MOLECULAR BIOLOGY 15 / 320 = 0.047 2024 Q1 T1 3.374 2024 Biochemistry 2024 Q1 Organic Chemistry 2024 Q1 Clinical Biochemistry 2024 Q1 19.5 2024 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Guarás, Adela Cabrera-Alarcón, José Luis Rivero, Maribel Universidad de Zaragoza Calvo, Enrique Rosa-Moreno, Marina Vázquez, Jesús Medina, Milagros Universidad de Zaragoza (orcid)0000-0001-8743-0182 Enríquez, José Antonio 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 69 (2024), 103001 [15 pp.] Redox biol. Redox Biology 2213-2317 10434208 http://zaguan.unizar.es/record/132790/files/texto_completo.pdf Versión publicada 2537825 http://zaguan.unizar.es/record/132790/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:132790 articulos driver 2026-02-17-20:18:32 ARTICLE