Research ArticlePhysiology

Acute O2 sensing through HIF2α-dependent expression of atypical cytochrome oxidase subunits in arterial chemoreceptors

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Science Signaling  21 Jan 2020:
Vol. 13, Issue 615, eaay9452
DOI: 10.1126/scisignal.aay9452

Breathing faster with HIF2α

In response to hypoxia, glomus cells in the carotid body trigger an increase in ventilation. At the molecular level, hypoxia slows down the electron transport chain in mitochondria, resulting in the accumulation of ROS and NADH, which ultimately activate glomus cells. HIF2α is a hypoxia-induced transcription factor that is highly abundant in glomus cells. Moreno-Domínguez et al. found that HIF2α was necessary for acute responses to hypoxia (see the Focus by Bishop and Ratcliffe). HIF2α mediated the expression of three atypical electron transport chain subunits that were necessary for a rapid buildup of ROS and NADH under hypoxic conditions in glomus cells. Similar to mice deficient in HIF2α in glomus cells, mice that lacked at least one of these atypical electron transport chain subunits in glomus cells also failed to increase ventilation in response to hypoxia. The authors propose that HIF2α target gene expression may set a tissue’s acute O2-sensing ability.

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