Bypassing mitochondrial complex III using alternative oxidase inhibits acute pulmonary oxygen sensing
Hypoxic pulmonary vasoconstriction
Hypoxia
Alternative oxidase
DOI:
10.1126/sciadv.aba0694
Publication Date:
2020-04-15T23:11:43Z
AUTHORS (24)
ABSTRACT
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.
SUPPLEMENTAL MATERIAL
Coming soon ....
REFERENCES (50)
CITATIONS (54)
EXTERNAL LINKS
PlumX Metrics
RECOMMENDATIONS
FAIR ASSESSMENT
Coming soon ....
JUPYTER LAB
Coming soon ....