Difference between revisions of "Curtabbi 2023 Redox Biol"
Line 14: | Line 14: | ||
|preparations=Permeabilized cells, Isolated mitochondria | |preparations=Permeabilized cells, Isolated mitochondria | ||
|enzymes=Complex I | |enzymes=Complex I | ||
|pathways=CIV | |couplingstates=OXPHOS | ||
|pathways=N, S, CIV | |||
|instruments=Oxygraph-2k | |instruments=Oxygraph-2k | ||
|additional=2024-01 | |additional=2024-01 | ||
}} | }} |
Revision as of 16:59, 2 January 2024
Curtabbi A, Guarás A, Cabrera-Alarcón JL, Rivero M, Calvo E, Rosa-Moreno M, Vázquez J, Medina M, Enríquez 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 Andrea, Guaras Adela, Cabrera-Alarcon Jose Luis, Rivero Maribel, Calvo Enrique, Rosa-Moreno Marina, Vazquez Jesus, Medina Milagros, Enriquez Jose Antonio (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. • Keywords: DPI, FMN, OXPHOS, Respiratory complex I • Bioblast editor: Plangger M
Labels: MiParea: Respiration, Pharmacology;toxicology
Organism: Mouse
Preparation: Permeabilized cells, Isolated mitochondria Enzyme: Complex I
Coupling state: OXPHOS Pathway: N, S, CIV HRR: Oxygraph-2k
2024-01