Sommer 2020 Sci Adv: Difference between revisions
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|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-1ฮฑ 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. | |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-1ฮฑ 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. | ||
|editor=[[Plangger M]] | |editor=[[Plangger M]] | ||
|mipnetlab=DE Giessen Weissmann N, FI Tampere Dufour E, FI Helsinki Jacobs HT | |mipnetlab=DE Giessen Weissmann N, FI Tampere Dufour E, FI Helsinki Jacobs HT, DE Jena Szibor M | ||
}} | }} | ||
{{Labeling | {{Labeling |
Revision as of 10:12, 8 June 2020
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 [Epub ahead of print]. |
ยป Open Access
Sommer N, Alebrahimdehkordi N, Pak O, Knoepp F, Strielkov I, Scheibe S, Dufour E, Andjelkovic 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) 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-1ฮฑ 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.
โข Bioblast editor: Plangger M โข O2k-Network Lab: DE Giessen Weissmann N, FI Tampere Dufour E, FI Helsinki Jacobs HT, DE Jena Szibor M
Labels: MiParea: Respiration
Stress:Hypoxia Organism: Rat Tissue;cell: Other cell lines Preparation: Intact cells
HRR: Oxygraph-2k
2020-04, AOX