Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 420, Issue 4, Pages 727-732Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2012.03.050
Keywords
Cytochrome c oxidase; Mitochondria; Hypoxia; Hypoxic inducible factor; Superoxide; Nitric oxide
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Funding
- National Institutes of Health [GM30228]
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The mitochondrial respiratory chain has been reported to play a role in the stabilization of HIF-1 alpha when mammalian cells experience hypoxia, most likely through the generation of free radicals. Although previous studies have suggested the involvement of superoxide catalyzed by complex III more recent studies raise the possibility that nitric oxide (NO) catalyzed by cytochrome c oxidase (Cco/NO), which functions in hypoxic signaling in yeast, may also be involved. Herein, we have found that HEK293 cells, which do not express a NOS isoform, possess Cco/NO activity and that this activity is responsible for an increase in intracellular NO levels when these cells are exposed to hypoxia. By using PTIO, a NO scavenger, we have also found that the increased NO levels in hypoxic HEK293 cells help stabilize HIF-1 alpha. These findings suggest a new mechanism for mitochondrial involvement in hypoxic signaling in mammalian cells. (C) 2012 Elsevier Inc. All rights reserved.
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