2024-03-29T01:27:40Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1541522017-08-18T00:53:40Zcom_10261_22com_10261_1com_10261_79col_10261_401col_10261_458
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Hernansanz-Agustín, Pablo
author
Ramos, Edurne
author
Navarro, Elisa
author
Parada, Esther
author
Moreno, Laura
author
Izquierdo-Álvarez, Alicia
author
Buendía Abaitua, Izaskun
author
Cogolludo, Angel
author
Egea Maiquez, Javier
author
López, Manuela G.
author
Martínez-Ruiz, Antonio
author
2016
Oxygen is a key molecule of aerobic life, but can give rise to reactive oxygen species (ROS) as metabolic byproducts of oxidative phosphorylation. Acute hypoxia produces a superoxide burst, which can signal downstream cell adaptations. Here we show that hypoxia triggers acute deactivation of mitochondrial complex I, changing its catalytic activity from an oxidoreductase to a Na+/H+ antiporter. The subsequent stimulation of mitochondrial Na+/Ca2+ exchanger (NCLX) activity promotes mitochondrial depolarization and superoxide production and underlies the participation of both
complex I and NCLX in acute oxygen sensing. NCLX inhibition is associated with the suppression of downstream ROS-driven responses to hypoxia such as hypoxic pulmonary vasoconstriction, HIF-1α stabilization and ischemic brain damage in vivo. These results provide biological explanations for superoxide production in acute hypoxia and highlight complex I and NCLX as potential therapeutic targets in diseases involving mitochondrial ROS signalling, hypoxia and oxidative stress.
3rd Symposium on Biomedical Research (2016)
http://hdl.handle.net/10261/154152
Reactive oxygen species production in acute hypoxia: oxygen sensing by mitochondrial complex I and the role of the sodium/calcium exchanger NCLX