Curtabbi 2023 Redox Biol
| Curtabbi A, GuarĂĄs A, Cabrera-AlarcĂłn JL, Rivero M, Calvo E, Rosa-Moreno M, VĂĄzquez J, Medina M, EnrĂquez JA (2023) Regulation of respiratory complex I assembly by FMN cofactor targeting. https://doi.org/10.1016/j.redox.2023.103001 |
» Redox Biol [Epub ahead of print]. PMID: 38145589 Open Access
Curtabbi A, GuarĂĄs A, Cabrera-AlarcĂłn JL, Rivero M, Calvo E, Rosa-Moreno M, VĂĄzquez J, Medina M, EnrĂquez JA (2023) Redox Biol
Abstract: 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.
âą Bioblast editor: Plangger M
Labels: MiParea: Respiration
HRR: Oxygraph-2k
2024-01
