2026-06-14T03:31:51Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/190372024-09-27T08:35:16Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Curtabbi, Andrea author Guaras, Adela author Cabrera-Alarcón, José Luis author Rivero, Maribel author Calvo, Enrique author Rosa-Moreno, Marina author Vazquez, Jesus author Medina, Milagros author Enriquez, Jose Antonio author 2024-02 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. Redox Biol. 2024 Feb:69:103001. 10.1016/j.redox.2023.103001 2213-2317 Redox biology 38145589 http://hdl.handle.net/20.500.12105/19037 Regulation of respiratory complex I assembly by FMN cofactor targeting.