Physiological Reviews, Vol 76, 839-885, Copyright © 1996 by American Physiological Society
Oxygen sensing and molecular adaptation to hypoxia
H. F. Bunn and R. O. Poyton
Division of Hematology/Oncology, Brigham and Women's Hospital, Harvard Medical School, Boston, Masachusetts, USA.
This review focuses on the molecular stratagems utilized by bacteria,
yeast, and mammals in their adaptation to hypoxia. Among this broad range
of organisms, changes in oxygen tension appear to be sensed by heme
proteins, with subsequent transfer of electrons along a signal transduction
pathway which may depend on reactive oxygen species. These heme-based
sensors are generally two-domain proteins. Some are hemokinases, while
others are flavohemoproteins [flavohemoglobins and NAD(P)H oxidases].
Hypoxia-dependent kinase activation of transcription factors in
nitrogen-fixing bacteria bears a striking analogy to the phosphorylation of
hypoxia inducible factor-1 (HIF-1) in mammalian cells. Moreover, redox
chemistry appears to play a critical role both in the trans-activation of
oxygen-responsive genes in unicellular organisms as well as in the
activation of HIF-1. In yeast and bacteria, regulatory operons coordinate
expression of genes responsible for adaptive responses to hypoxia and
hyperoxia. Similarly, in mammals, combinatorial interactions of HIF-1 with
other identified transcription factors are required for the hypoxic
induction of physiologically important genes.
