Difference between revisions of "Curtabbi 2023 Redox Biol"
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|keywords=DPI, FMN, OXPHOS, Respiratory complex I | |keywords=DPI, FMN, OXPHOS, Respiratory complex I | ||
|editor=[[Plangger M]] | |editor=[[Plangger M]] | ||
|mipnetlab=ES Madrid Enriquez JA | |||
}} | }} | ||
{{Labeling | {{Labeling | ||
|area=Respiration, Pharmacology;toxicology | |area=Respiration, Genetic knockout;overexpression, Pharmacology;toxicology | ||
|organism=Mouse | |||
|tissues=Kidney, Fibroblast | |||
|preparations=Permeabilized cells, Isolated mitochondria | |||
|enzymes=Complex I | |enzymes=Complex I | ||
|couplingstates=OXPHOS | |||
|pathways=N, S, CIV | |||
|instruments=Oxygraph-2k | |instruments=Oxygraph-2k | ||
|additional=2024-01 | |additional=2024-01 | ||
}} | }} |
Latest revision as of 15:35, 3 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 • O2k-Network Lab: ES Madrid Enriquez JA
Labels: MiParea: Respiration, Genetic knockout;overexpression, Pharmacology;toxicology
Organism: Mouse
Tissue;cell: Kidney, Fibroblast
Preparation: Permeabilized cells, Isolated mitochondria
Enzyme: Complex I
Coupling state: OXPHOS Pathway: N, S, CIV HRR: Oxygraph-2k
2024-01