Hernansanz-Agustin 2020 Nature

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Hernansanz-Agustín P, Choya-Foces C, Carregal-Romero S, Ramos E, Oliva T, Villa-Piña T, Moreno L, Izquierdo-Álvarez A, Cabrera-García JD, Cortés A, Lechuga-Vieco AV, Jadiya P, Navarro E, Parada E, Palomino-Antolín A, Tello D, Acín-Pérez R, Rodríguez-Aguilera JC, Navas P, Cogolludo Á, López-Montero I, Martínez-Del-Pozo Á, Egea J, López MG, Elrod JW, Ruíz-Cabello J, Bogdanova A, Enríquez JA, Martínez-Ruiz A (2020) Na+ controls hypoxic signalling by the mitochondrial respiratory chain. Nature [Epub ahead of print].

» PMID: 32728214

Hernansanz-Agustin Pablo, Choya-Foces Carmen, Carregal-Romero Susana, Ramos Elena, Oliva Tamara, Villa-Pina Tamara, Moreno Laura, Izquierdo-Alvarez Alicia, Cabrera-Garcia J Daniel, Cortes Ana, Lechuga-Vieco Ana Victoria, Jadiya Pooja, Navarro Elisa, Parada Esther, Palomino-Antolin Alejandra, Tello Daniel, Acin-Perez Rebeca, Rodriguez-Aguilera Juan Carlos, Navas Placido, Cogolludo Angel, Lopez-Montero Ivan, Martinez-Del-Pozo Alvaro, Egea Javier, Lopez Manuela G, Elrod John W, Ruiz-Cabello Jesus, Bogdanova Anna, Enríquez Jose Antonio, Martinez-Ruiz Antonio (2020) Nature

Abstract: 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 adaptations, a phenomenon that occurs in hypoxia and whose precise mechanism remains unknown. Ca2+ is the best known ion that acts as a second messenger, yet the role ascribed to Na+ is to serve as a mere mediator of membrane potential. 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 hypoxia 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.


Bioblast editor: Plangger M


Labels: MiParea: Respiration, mt-Membrane 

Stress:Oxidative stress;RONS, Hypoxia  Organism: Rat  Tissue;cell: Heart  Preparation: Isolated mitochondria 

Regulation: Ion;substrate transport 


HRR: Oxygraph-2k, O2k-Fluorometer 

2020-08, AmR