Mitochondria have various essential functions in metabolism and in determining cell fate during apoptosis. In addition, mitochondria are also important nodes in a number of signaling pathways. For example, mitochondria can modulate signals transmitted by second messengers such as
calcium. Because mitochondria are also major sources of
reactive oxygen species (ROS), they can contribute to redox signaling--for example, by the production of ROS such as
hydrogen peroxide that can reversibly modify
cysteine residues and thus the activity of target
proteins. Mitochondrial ROS production is thought to play a role in
hypoxia signaling by stabilizing the
oxygen-sensitive
transcription factor hypoxia-inducible factor-1α. New evidence has extended the mechanism of mitochondrial redox signaling in cellular responses to
hypoxia in interesting and unexpected ways.
Hypoxia altered the microtubule-dependent transport of mitochondria so that the organelles accumulated in the perinuclear region, where they increased the intranuclear concentration of ROS. The increased ROS in turn enhanced the expression of
hypoxia-sensitive genes such as
VEGF (
vascular endothelial growth factor) not by reversibly oxidizing a
protein, but by oxidizing DNA sequences in the
hypoxia response element of the
VEGF promoter. This paper and other recent work suggest a new twist on mitochondrial signaling: that the redistribution of mitochondria within the cell can be a component of regulatory pathways.