Bypassing mitochondrial complex III using alternative oxidase inhibits acute pulmonary oxygen sensing

• DOI: 10.1126/sciadv.aba0694
• Publication Date: 2020-04-15T23:11:43Z
• Authors: Natascha Sommer; Nasim Alebrahimde...; Oleg Pak; Fenja Knoepp; Ievgen Strielkov; Susan Scheibe; Eric Dufour; Ana Andjelković; Akylbek Sydykov; Alireza Saraji; Aleksandar Petrovic; Karin Quanz; Matthias Hecker; Manish Kumar; Joel Wahl; Simone Kraut; Werner Seeger; Ralph T. Schermuly; Hossein A. Ghofrani; Kerstin Ramser; Thomas Braun; Howard T. Jacobs; Norbert Weissmann; Marten Szibor
• Keywords: Hypoxic pulmonary vasoconstriction; Hypoxia; Alternative oxidase

Mitochondria play an important role in sensing both acute and chronic hypoxia the pulmonary vasculature, but their primary oxygen-sensing mechanism contribution to stabilization of hypoxia-inducible factor (HIF) remains elusive. Alteration mitochondrial electron flux increased superoxide release from complex III has been proposed as essential trigger for hypoxic vasoconstriction (HPV). We used mice expressing a tunicate alternative oxidase, AOX, which maintains when respiratory complexes and/or IV are inhibited. Respiratory restoration by AOX prevented HPV responses arterial smooth muscle cells (PASMC), hypoxia-induced redox changes NADH cytochrome c, production. In contrast, did not affect development hypertension HIF-1α stabilization. These results indicate that distal inhibition transport chain PASMC is initial step oxygen sensing.