000132790 001__ 132790
000132790 005__ 20250923084411.0
000132790 0247_ $$2doi$$a10.1016/j.redox.2023.103001
000132790 0248_ $$2sideral$$a137761
000132790 037__ $$aART-2024-137761
000132790 041__ $$aeng
000132790 100__ $$aCurtabbi, Andrea
000132790 245__ $$aRegulation of respiratory complex I assembly by FMN cofactor targeting
000132790 260__ $$c2024
000132790 5060_ $$aAccess copy available to the general public$$fUnrestricted
000132790 5203_ $$aRespiratory 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.
000132790 536__ $$9info:eu-repo/grantAgreement/ES/DGA/E35-23R$$9info:eu-repo/grantAgreement/ES/MICINN/PID2021-127988OB-I00$$9info:eu-repo/grantAgreement/ES/MICINN/PID2022-136369NB-I00$$9info:eu-repo/grantAgreement/ES/MICINN/TED2021-131611B-I00
000132790 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttp://creativecommons.org/licenses/by-nc-nd/3.0/es/
000132790 590__ $$a11.9$$b2024
000132790 592__ $$a3.374$$b2024
000132790 591__ $$aBIOCHEMISTRY & MOLECULAR BIOLOGY$$b15 / 319 = 0.047$$c2024$$dQ1$$eT1
000132790 593__ $$aBiochemistry$$c2024$$dQ1
000132790 593__ $$aOrganic Chemistry$$c2024$$dQ1
000132790 593__ $$aClinical Biochemistry$$c2024$$dQ1
000132790 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000132790 700__ $$aGuarás, Adela
000132790 700__ $$aCabrera-Alarcón, José Luis
000132790 700__ $$aRivero, Maribel$$uUniversidad de Zaragoza
000132790 700__ $$aCalvo, Enrique
000132790 700__ $$aRosa-Moreno, Marina
000132790 700__ $$aVázquez, Jesús
000132790 700__ $$0(orcid)0000-0001-8743-0182$$aMedina, Milagros$$uUniversidad de Zaragoza
000132790 700__ $$aEnríquez, José Antonio
000132790 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000132790 773__ $$g69 (2024), 103001 [15 pp.]$$pRedox biol.$$tRedox Biology$$x2213-2317
000132790 8564_ $$s10434208$$uhttps://zaguan.unizar.es/record/132790/files/texto_completo.pdf$$yVersión publicada
000132790 8564_ $$s2537825$$uhttps://zaguan.unizar.es/record/132790/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000132790 909CO $$ooai:zaguan.unizar.es:132790$$particulos$$pdriver
000132790 951__ $$a2025-09-22-14:30:08
000132790 980__ $$aARTICLE