| Mitochondrial respiration protects against oxygen-associated DNA damage. | |
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MedLine Citation:
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PMID: 20975668 Owner: NLM Status: In-Process |
Abstract/OtherAbstract:
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Oxygen is not only required for oxidative phosphorylation but also serves as the essential substrate for the formation of reactive oxygen species (ROS), which is implicated in ageing and tumorigenesis. Although the mitochondrion is known for its bioenergetic function, the symbiotic theory originally proposed that it provided protection against the toxicity of increasing oxygen in the primordial atmosphere. Using human cells lacking Synthesis of Cytochrome c Oxidase 2 (SCO2-/-), we have tested the oxygen toxicity hypothesis. These cells are oxidative phosphorylation defective and glycolysis dependent; they exhibit increased viability under hypoxia and feature an inverted growth response to oxygen compared with wild-type cells. SCO2-/- cells have increased intracellular oxygen and nicotinamide adenine dinucleotide (NADH) levels, which result in increased ROS and oxidative DNA damage. Using this isogenic cell line, we have revealed the genotoxicity of ambient oxygen. Our study highlights the importance of mitochondrial respiration both for bioenergetic benefits and for maintaining genomic stability in an oxygen-rich environment. |
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Authors:
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Ho Joong Sung; Wenzhe Ma; Ping-Yuan Wang; James Hynes; Tomas C O'Riordan; Christian A Combs; J Philip McCoy; Fred Bunz; Ju-Gyeong Kang; Paul M Hwang |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Nature communications Volume: 1 ISSN: 2041-1723 ISO Abbreviation: Nat Commun Publication Date: 2010 Apr |
Date Detail:
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Created Date: 2010-10-26 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101528555 Medline TA: Nat Commun Country: England |
Other Details:
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Languages: eng Pagination: 1-8 Citation Subset: IM |
Affiliation:
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Translational Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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