Send to:

Choose Destination
See comment in PubMed Commons below
Histochem Cell Biol. 2005 Jul;124(1):69-76. Epub 2005 Jul 22.

Role of mitochondria in the regulation of hypoxia-inducible factor-1alpha in the rat carotid body glomus cells.

Author information

  • 1Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6085, USA.


Hypoxia-inducible factor-1alpha (HIF-1alpha) protein, a heterodimeric transcription factor that regulates transcriptional activation of several genes, is involved in adaptive responses to hypoxia. Earlier, we have reported that in carotid body (CB), the peripheral oxygen sensing organ, HIF-1alpha is up-regulated during hypoxia. One model proposes that an intact mitochondrial respiratory chain is necessary for this regulation of HIF-1alpha. To test this hypothesis in the CB glomus cells, we studied the effect of mitochondrial electron transport chain (ETC) inhibitors: rotenone (complex I; 1 microM), malonate (complex II; 0.5 M), antimycin A (complex III; 1 microg/ml), sodium azide (complex IV; 5 mM), and uncoupler of oxidative phosphorylation: carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP; 1 mM) on HIF-1alpha expression during normoxia and hypoxia. Inhibitors and uncoupler of mitochondrial ETC abrogated hypoxia-induced HIF-1alpha expression in isolated glomus cells significantly (P < 0.001). Effect of rotenone during hypoxia was abolished by succinate (4 mM), a substrate for complex II. Further, HIF-1alpha expression was not altered by any of these mitochondrial inhibitors during normoxia. Taken together, these results strongly indicate that a functional mitochondrial ETC is required for the stabilization of HIF-1alpha, and further the connection between HIF-1alpha and mitochondria in CB oxygen sensing is reiterated.

[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Springer
    Loading ...
    Write to the Help Desk