Sommer 2020 Sci Adv
|Sommer N, Alebrahimdehkordi N, Pak O, Knoepp F, Strielkov I, Scheibe S, Dufour E, Andjelekovic A, Sydykov A, Saraji A, Petrovic A, Quanz K, Hecker M, Kumar M, Wahl J, Kraut S, Seeger W, Schermuly RT, Ghofrani HA, Ramser K, Braun T, Jacobs HT, Weissmann N, Szibor M (2020) Bypassing mitochondrial complex III using alternative oxidase inhibits acute pulmonary oxygen sensing. Sci Adv 6:eaba0694.|
Sommer Natascha, Alebrahimdehkordi Nasim, Pak Oleg, Knoepp Fenja, Strielkov Ievgen, Scheibe Susan, Dufour Eric, Andjelkovic Ana, Sydykov Akylbek, Saraji Alireza, Petrovic Aleksandar, Quanz Karin, Hecker Matthias, Kumar Manish, Wahl Joel, Kraut Simone, Seeger Werner, Schermuly Ralph T, Ghofrani Hossein A, Ramser Kerstin, Braun Thomas, Jacobs Howard T, Weissmann Norbert, Szibor Marten (2020) Sci Adv
Abstract: Mitochondria play an important role in sensing both acute and chronic hypoxia in the pulmonary vasculature, but their primary oxygen-sensing mechanism and contribution to stabilization of the hypoxia-inducible factor (HIF) remains elusive. Alteration of the mitochondrial electron flux and increased superoxide release from complex III has been proposed as an essential trigger for hypoxic pulmonary vasoconstriction (HPV). We used mice expressing a tunicate alternative oxidase, AOX, which maintains electron flux when respiratory complexes III and/or IV are inhibited. Respiratory restoration by AOX prevented acute HPV and hypoxic responses of pulmonary arterial smooth muscle cells (PASMC), acute hypoxia-induced redox changes of NADH and cytochrome c, and superoxide production. In contrast, AOX did not affect the development of chronic hypoxia-induced pulmonary hypertension and HIF-1α stabilization. These results indicate that distal inhibition of the mitochondrial electron transport chain in PASMC is an essential initial step for acute but not chronic oxygen sensing.
Labels: MiParea: Respiration
Stress:Hypoxia Organism: Rat Tissue;cell: Other cell lines Preparation: Intact cells