Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 276, Issue 25, Pages 21995-21998Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.C100177200
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Funding
- NCI NIH HHS [R01 CA089212, K01 CA098809, 1RO1 CA89212-02] Funding Source: Medline
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Hypoxia induces the stabilization and transcriptional activation of the hypoxia-inducible factor 1 alpha (HIF-1 alpha) protein, the regulatory member of the HIF-1 complex, The molecular mechanisms that are responsible for oxygen sensing and the downstream pathways utilized by the hypoxic signal are still poorly understood, One hypothesis for oxygen sensing has postulated that reactive oxygen species generated at mitochondrial complex III are the initiators of the hypoxic signal. Here we find that mitochondrial DNA-less (rho degrees) cells have a normal response to hypoxia, measured at the level of HIF-1 alpha protein stabilization, nuclear translocation, and its transcriptional activation activity. Furthermore, overexpression of catalase, either in the mitochondria or in the cytosol, fails to modify the hypoxia response indicating that hydrogen peroxide is not a signaling molecule in the hypoxic signaling cascade that culminates with HIF-1 activation.
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