Cells respond to hypoxia over different timescales. Although the HIF transcriptional pathway mediates many of these cellular responses to hypoxia, it cannot account for rapid responses that occur within seconds of exposure, for example, the electrophysiological events that take place in the carotid body termed oxygen chemosensitivity, triggering hyperventilation in response to hypoxia.
Findings from the hypoxia laboratory (led by Peter Ratcliffe, Tom Keeley and Tammie Bishop) establish that activation of the HIF transcriptional pathway, in particular one isoform: HIF-2α, is sufficient to induce this property in chromaffin cells of the adult adrenal medulla – an organ that is related to the carotid body but not normally oxygen chemosensitive in the adult.
This work links to two major oxygen sensing systems: HIF transcription and oxygen chemosensitivity. Further, since activating mutations in the HIF pathway are commonly observed in chromaffin cell tumours (paragangliomas or PGLs), these findings raise questions as to the importance of oxygen chemosensitivity in these and other secretory cancers. For example, oxygen chemosensitivity may contribute to the clinical symptomatology of PGLs and/or directly contribute to oncogenic drive. This work therefore highlights the (new) potential for linking electrophysiological oxygen chemosensitivity to oncogenic drive in certain tissues.
To learn more, read the full article at the Journal of Clinical Investigation.