Reactive Oxygen Species–Mediated Mitochondria-to-Nucleus Signaling: A Key to Aging and Radical-Caused Diseases
Abstract
Mitochondria-generated reactive oxygen species have been implicated as a common feature that connects aging of organisms and age-related diseases. Efficient elimination of these radicals by antioxidants correlates with increased life span. Understanding how the mitochondrion signals to the nucleus to regulate antioxidant proteins might be a key to aging processes and treatment of human diseases.
Abstract
The mitochondrial respiratory chain generates reactive oxygen species (ROS), oxygen-containing molecules that are chemically reactive because they contain unpaired electrons, as a by-product of aerobic metabolism. These ROS are rapidly detoxified by antioxidant proteins. The failure of effective detoxification of cells from mROS contributes to aging and has been implicated in the development and progression of age-related diseases. ROS can be decreased by dietary antioxidants or by antioxidant proteins, which are encoded by nuclear genes. Because the source of ROS and the location of gene regulation are separated, mitochondria-to-nucleus signaling is thought to regulate cellular detoxification. Notable advances have been made in identifying the protective signaling pathways that are activated by increased intracellular oxidant levels. There is increasing evidence that protein oxidation directly regulates phosphatases and kinases. Some of these signaling molecules appear to function as ROS sensors that initiate signaling from the mitochondria to the nucleus. Understanding how the mitochondrion signals to the nucleus to regulate antioxidant proteins might be useful in efforts to extend life span in humans or to improve treatments for neurodegenerative or other diseases influenced by ROS.
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I thank E. A. Thompson and H. Doeppler for their helpful comments on the manuscript. Research in the Storz laboratory is funded by the Mayo Clinic Cancer Center.
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