Na+ controls hypoxic signalling by the mitochondrial respiratory chain
| العنوان: | Na+ controls hypoxic signalling by the mitochondrial respiratory chain |
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| المؤلفون: | Jesús Ruiz-Cabello, Álvaro Martínez-del-Pozo, Pooja Jadiya, Angel Cogolludo, Elisa Navarro, Elena Ramos, Antonio Martínez-Ruiz, Carmen Choya-Foces, Ana Cortés, Susana Carregal-Romero, José Antonio Enríquez, John W. Elrod, Esther Parada, Iván López-Montero, Alejandra Palomino-Antolín, J. Daniel Cabrera-García, Tamara Villa-Piña, Javier Egea, Alicia Izquierdo-Álvarez, Daniel Tello, Anna Bogdanova, Pablo Hernansanz-Agustín, Plácido Navas, Laura Moreno, Juan Carlos Rodríguez-Aguilera, Tamara Oliva, Manuela G. López, Ana Victoria Lechuga-Vieco, Rebeca Acín-Pérez |
| المساهمون: | University of Zurich, Enríquez, José Antonio, Martínez-Ruiz, Antonio, Instituto de Salud Carlos III, Agencia Estatal de Investigación (España), European Commission, Ministerio de Ciencia, Innovación y Universidades (España), Comunidad de Madrid, Fundación Domingo Martínez, Human Frontier Science Program, Fundación BBVA, Banco Santander, Universidad Complutense de Madrid, Eusko Jaurlaritza, Swiss National Science Foundation, Universidad Autónoma de Madrid |
| المصدر: | Repisalud Instituto de Salud Carlos III (ISCIII) Nature Digital.CSIC. Repositorio Institucional del CSIC instname |
| بيانات النشر: | Springer Science and Business Media LLC, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Calcium Phosphates, Male, 0301 basic medicine, Membrane Fluidity, Breast Neoplasms, Oxidative phosphorylation, Second Messenger Systems, Article, Oxidative Phosphorylation, Sodium-Calcium Exchanger, Electron Transport, Mitochondrial Proteins, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Cell Line, Tumor, Membrane fluidity, Animals, Chemical Precipitation, Humans, Rats, Wistar, Hypoxia, Inner mitochondrial membrane, Calcium signaling, chemistry.chemical_classification, 1000 Multidisciplinary, Reactive oxygen species, Multidisciplinary, Superoxide, Sodium, 10081 Institute of Veterinary Physiology, Mitochondria, Rats, 3. Good health, Mice, Inbred C57BL, 030104 developmental biology, Mitochondrial respiratory chain, chemistry, Coenzyme Q – cytochrome c reductase, Mitochondrial Membranes, Biophysics, 570 Life sciences, biology, Reactive Oxygen Species, 030217 neurology & neurosurgery |
| الوصف: | All metazoans depend on the consumption of O2 by the mitochondrial oxidative phosphorylation system (OXPHOS) to produce energy. In addition, the OXPHOS uses O2 to produce reactive oxygen species that can drive cell adaptations1,2,3,4, a phenomenon that occurs in hypoxia4,5,6,7,8 and whose precise mechanism remains unknown. Ca2+ is the best known ion that acts as a second messenger9, yet the role ascribed to Na+ is to serve as a mere mediator of membrane potential10. Here we show that Na+ acts as a second messenger that regulates OXPHOS function and the production of reactive oxygen species by modulating the fluidity of the inner mitochondrial membrane. A conformational shift in mitochondrial complex I during acute hypoxia11 drives acidification of the matrix and the release of free Ca2+ from calcium phosphate (CaP) precipitates. The concomitant activation of the mitochondrial Na+/Ca2+ exchanger promotes the import of Na+ into the matrix. Na+ interacts with phospholipids, reducing inner mitochondrial membrane fluidity and the mobility of free ubiquinone between complex II and complex III, but not inside supercomplexes. As a consequence, superoxide is produced at complex III. The inhibition of Na+ import through the Na+/Ca2+ exchanger is sufficient to block this pathway, preventing adaptation to hypoxia. These results reveal that Na+ controls OXPHOS function and redox signalling through an unexpected interaction with phospholipids, with profound consequences for cellular metabolism. This research has been financed by Spanish Government grants (ISCIII and AEI agencies, partially funded by the European Union FEDER/ERDF) CSD2007-00020 (RosasNet, Consolider-Ingenio 2010 programme to A.M.-R. and J.A.E.); CP07/00143, PS09/00101, PI12/00875, PI15/00107 and RTI2018-094203-B-I00 (to A.M.-R.); CP12/03304 and PI15/01100 (to L.M.); CP14/00008, CPII19/00005 and PI16/00735 (to J.E.); SAF2016-77222-R (to A. Cogolludo); PI17/01286 (to P.N.); SAF2015-65633-R, RTI2018-099357-B-I00 and CB16/10/00282 (to J.A.E.); RTI2018-095793-B-I00 (to M.G.L.); and SAF2017-84494-2-R (to J.R.-C.), by the European Union (ITN GA317433 to J.A.E. and MC-CIG GA304217 to R.A.-P.), by grants from the Comunidad de Madrid B2017/BMD-3727 (to A. Cogolludo) and B2017/BMD-3827 (to M.G.L.), by a grant from the Fundación Domingo Martínez (to M.G.L. and A.M.-R.), by the Human Frontier Science Program grant HFSP-RGP0016/2018 (to J.A.E.), by grants from the Fundación BBVA (to R.A.-P. and J.R.-C.), by the UCM-Banco Santander grant PR75/18-21561 (to A.M.-d.-P.), by the Programa Red Guipuzcoana de Ciencia, Tecnología e Información 2018-CIEN-000058-01 (to J.R.-C.) and from the Basque Government under the ELKARTEK Program (grant no. KK-2019/bmG19 to J.R.-C.), by the Swiss National Science Foundation (SNF) grant 310030_124970/1 (to A.B.), by a travel grant from the IIS-IP (to P.H.-A.) and by the COST actions TD0901 (HypoxiaNet) and BM1203 (EU-ROS). The CNIC is supported by the Pro-CNIC Foundation and is a Severo Ochoa Center of Excellence (Spanish Government award SEV-2015-0505). CIC biomaGUNE is supported by the María de Maeztu Units of Excellence Program from the Spanish Government (MDM-2017-0720). P.H.-A. was a recipient of a predoctoral FPU fellowship from the Spanish Government. E.N. is a recipient of a predoctoral FPI fellowship from the Universidad Autónoma de Madrid (UAM). A.M.-R., L.M. and J.E. are supported by the I3SNS or ‘Miguel Servet’ programmes (ISCIII, Spanish Government; partially funded by the FEDER/ERDF). |
| وصف الملف: | Hernansanz-Agustin_Nature_2020.pdf - application/pdf |
| تدمد: | 1476-4687 0028-0836 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3f9e908db6fcb4baf1f18fb0e4ce89c4 https://doi.org/10.1038/s41586-020-2551-y |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....3f9e908db6fcb4baf1f18fb0e4ce89c4 |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 14764687 00280836 |
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