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Science 5 October 2007:
Vol. 318. no. 5847, pp. 62 - 64
DOI: 10.1126/science.1147949
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Perspective

Life with Oxygen

Gregg L. Semenza

The survival of all metazoan organisms is dependent on the regulation of O2 delivery and utilization to maintain a balance between the generation of energy and production of potentially toxic oxidants. Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that functions as a master regulator of oxygen homeostasis and has essential roles in metazoan development, physiology, and disease pathogenesis. Remarkable progress has been made in delineating the molecular mechanisms whereby changes in cellular oxygenation are transduced to the nucleus as changes in gene transcription through the activity of HIF-1. Pharmacologic agents that activate or inhibit the hypoxia signal transduction pathway may be useful therapies for ischemic and neoplastic disorders, respectively, which are the major causes of mortality in industrialized societies.

Vascular Program, Institute for Cell Engineering; Departments of Pediatrics, Medicine, Oncology, Radiation Oncology; and McKusick-Nathans Institute of Genetic Medicine; The Johns Hopkins University School of Medicine, Broadway Research Building, Suite 671, 733 North Broadway, Baltimore, MD 21205, USA. E-mail: gsemenza{at}jhmi.edu

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