Topics:
Basic Science
Session number: 702
Session title: Response and adaptation to stress
Authors: Schumacker, Paul (Chicago, US)
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Cells respond to moderate hypoxia by activating protective mechanisms. These include the expression of new genes, largely achieved through activation of the transcription factor Hypoxia-Inducible Factor (HIF). In addition, cells activate post-translational adaptive responses. The cellular mechanisms that detect the hypoxia and trigger these responses are not well established. We propose that Reactive Oxygen Species (ROS) signals, originating from the mitochondrial electron transport chain, signal the onset of hypoxia and trigger diverse adaptive responses in cells. Unlike the damaging levels of excessive oxidant stress generated in response to ischemia, these low levels of ROS signaling are well tolerated and are released to the cytosol. The resulting oxidant signaling is both necessary and sufficient to activate the cellular response to hypoxia.
Teaching objective of the lecture:
Understand the sites of ROS production in cells
Understand how ROS signals can trigger diverse responses to hypoxia
Appreciate how genetic models can be used to dissect the sites of ROS production from the mitochondrial electron transport chain
Understand how ROS signals are compartmentalized within cells.
Take home messages
- Mitochondria function to produce ATP in cells, and they also function to signal stresses such as hypoxia
- Although high levels of ROS production can induce cellular oxidative damage, low signaling levels of ROS play important roles in regulating cell responses to stress
- Broad spectrum antioxidants, when administered to attenuate excessive oxidant stress, also disrupt normal oxidant signaling pathways.
The content of this article reflects the personal opinion of the
author/s and is not necessarily the official position of the
European Society of Cardiology.