This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bell, E. L.
Right arrow Articles by Chandel, N. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bell, E. L.
Right arrow Articles by Chandel, N. S.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, August 2007, p. 5737-5745, Vol. 27, No. 16
0270-7306/07/$08.00+0     doi:10.1128/MCB.02265-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Mitochondrial Reactive Oxygen Species Trigger Hypoxia-Inducible Factor-Dependent Extension of the Replicative Life Span during Hypoxia{triangledown}

Eric L. Bell,1 Tatyana A. Klimova,1 James Eisenbart,1 Paul T. Schumacker,1,2 and Navdeep S. Chandel1*

Department of Medicine and Cell and Molecular Biology, The Feinberg School of Medicine, Northwestern University, Chicago, Illinois, 60611,1 Department of Pediatrics, The Feinberg School of Medicine, Northwestern University, Chicago, Illinois, 606112

Received 4 December 2006/ Returned for modification 11 January 2007/ Accepted 25 May 2007

Physiological hypoxia extends the replicative life span of human cells in culture. Here, we report that hypoxic extension of replicative life span is associated with an increase in mitochondrial reactive oxygen species (ROS) in primary human lung fibroblasts. The generation of mitochondrial ROS is necessary for hypoxic activation of the transcription factor hypoxia-inducible factor (HIF). The hypoxic extension of replicative life span is ablated by a dominant negative HIF. HIF is sufficient to induce telomerase reverse transcriptase mRNA and telomerase activity and to extend replicative life span. Furthermore, the down-regulation of the von Hippel-Lindau tumor suppressor protein by RNA interference increases HIF activity and extends replicative life span under normoxia. These findings provide genetic evidence that hypoxia utilizes mitochondrial ROS as signaling molecules to activate HIF-dependent extension of replicative life span.

* Corresponding author. Mailing address: Department of Cell and Molecular Biology, Northwestern University Medical School, McGaw Pavilion, 240 East Huron Avenue, M-334, Chicago, IL 60611. Phone: (312) 503-2549. Fax: (312) 908-8163. E-mail: nav{at}northwestern.edu

{triangledown} Published ahead of print on 11 June 2007.

Molecular and Cellular Biology, August 2007, p. 5737-5745, Vol. 27, No. 16
0270-7306/07/$08.00+0     doi:10.1128/MCB.02265-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Chen, R.-Q., Yang, Q.-K., Chen, Y.-L., Oliveira, V. A., Dalton, W. S., Fearns, C., Lee, J.-D. (2009). Kinome Sirna Screen Identifies SMG-1 as a Negative Regulator of Hypoxia-inducible Factor-1{alpha} in Hypoxia. J. Biol. Chem. 284: 16752-16758 [Abstract] [Full Text]  
  • Klimova, T. A., Bell, E. L., Shroff, E. H., Weinberg, F. D., Snyder, C. M., Dimri, G. P., Schumacker, P. T., Budinger, G. R. S., Chandel, N. S. (2009). Hyperoxia-induced premature senescence requires p53 and pRb, but not mitochondrial matrix ROS. FASEB J. 23: 783-794 [Abstract] [Full Text]  
  • Bencokova, Z., Kaufmann, M. R., Pires, I. M., Lecane, P. S., Giaccia, A. J., Hammond, E. M. (2009). ATM Activation and Signaling under Hypoxic Conditions. Mol. Cell. Biol. 29: 526-537 [Abstract] [Full Text]  
  • Qutub, A. A., Popel, A. S. (2008). Reactive Oxygen Species Regulate Hypoxia-Inducible Factor 1{alpha} Differentially in Cancer and Ischemia. Mol. Cell. Biol. 28: 5106-5119 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»