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
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.
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