Difference between revisions of "Curtabbi 2023 Redox Biol"
(Created page with "{{Publication |title=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...") Â |
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|title=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 | |title=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 | ||
|info=Redox Biol [Epub ahead of print]. [https://pubmed.ncbi.nlm.nih.gov/38145589 PMID: 38145589 Open Access] | |info=Redox Biol [Epub ahead of print]. [https://pubmed.ncbi.nlm.nih.gov/38145589 PMID: 38145589 Open Access] | ||
|authors=Curtabbi | |authors=Curtabbi Andrea, Guaras Adela, Cabrera-Alarcon Jose Luis, Rivero Maribel, Calvo Enrique, Rosa-Moreno Marina, Vazquez Jesus, Medina Milagros, Enriquez Jose Antonio | ||
|year=2023 | |year=2023 | ||
|journal=Redox Biol | |journal=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. | |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 | |||
|editor=[[Plangger M]] | |editor=[[Plangger M]] | ||
}} | }} | ||
{{Labeling | {{Labeling | ||
|area=Respiration | |area=Respiration | ||
|enzymes=Complex I | |||
|instruments=Oxygraph-2k | |instruments=Oxygraph-2k | ||
|additional=2024-01 | |additional=2024-01 | ||
}} | }} |
Revision as of 16:19, 2 January 2024
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 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. âą Keywords: DPI, FMN, OXPHOS, Respiratory complex I âą Bioblast editor: Plangger M
Labels: MiParea: Respiration
Enzyme: Complex I
HRR: Oxygraph-2k
2024-01