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Mol. Biol. Cell 21 (1): 212-217

Copyright © 2010 by The American Society for Cell Biology.

Hydrogen Sulfide Increases Hypoxia-inducible Factor-1 Activity Independently of von Hippel–Lindau Tumor Suppressor-1 in C. elegans

Mark W. Budde, and Mark B. Roth

Division of Basic Sciences, Fred Hutchinson Cancer Research Center; and Molecular and Cellular Biology Program, University of Washington, Seattle, WA 98109

Received for publication March 11, 2009. Revision received October 9, 2009. Accepted for publication October 23, 2009.

Monitoring Editor: William P. Tansey

Abstract: Rapid alteration of gene expression in response to environmental changes is essential for normal development and behavior. The transcription factor hypoxia-inducible factor (HIF)-1 is well known to respond to alterations in oxygen availability. In nature, low oxygen environments are often found to contain high levels of hydrogen sulfide (H2S). Here, we show that Caenorhabditis elegans can have mutually exclusive responses to H2S and hypoxia, both involving HIF-1. Specifically, H2S results in HIF-1 activity throughout the hypodermis, whereas hypoxia causes HIF-1 activity in the gut as judged by a reporter for HIF-1 activity. C. elegans require hif-1 to survive in room air containing trace amounts of H2S. Exposure to H2S results in HIF-1 nuclear localization and transcription of HIF-1 targets. The effects of H2S on HIF-1 reporter activity are independent of von Hippel–Lindau tumor suppressor (VHL)-1, whereas VHL-1 is required for hypoxic regulation of HIF-1 reporter activity. Because H2S is naturally produced by animal cells, our results suggest that endogenous H2S may influence HIF-1 activity.

This was published online ahead of print in MBC in Press ( on November 4, 2009.

Address correspondence to: Mark B. Roth (mroth{at}

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