| Forty percent methionine restriction decreases mitochondrial oxygen radical production and leak at complex I during forward electron flow and lowers oxidative damage to proteins and mitochondrial DNA in rat kidney and brain mitochondria. | |
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MedLine Citation:
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PMID: 20041736 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Eighty percent dietary methionine restriction (MetR) in rodents (without calorie restriction), like dietary restriction (DR), increases maximum longevity and strongly decreases mitochondrial reactive oxygen species (ROS) production and oxidative stress. Eighty percent MetR also lowers the degree of membrane fatty acid unsaturation in rat liver. Mitochondrial ROS generation and the degree of fatty acid unsaturation are the only two known factors linking oxidative stress with longevity in vertebrates. However, it is unknown whether 40% MetR, the relevant methionine restriction degree to clarify the mechanisms of action of standard (40%) DR can reproduce these effects in mitochondria from vital tissues of strong relevance for aging. Here we study the effect of 40% MetR on ROS production and oxidative stress in rat brain and kidney mitochondria. Male Wistar rats were fed during 7 weeks semipurified diets differing only in their methionine content: control or 40% MetR diets. It was found that 40% MetR decreases mitochondrial ROS production and percent free radical leak (by 62-71%) at complex I during forward (but not during reverse) electron flow in both brain and kidney mitochondria, increases the oxidative phosphorylation capacity of brain mitochondria, lowers oxidative damage to kidney mitochondrial DNA, and decreases specific markers of mitochondrial protein oxidation, lipoxidation, and glycoxidation in both tissues. Forty percent MetR also decreased the amount of respiratory complexes I, III, and IV and apoptosis-inducing factor (AIF) in brain mitochondria and complex IV in kidney mitochondria, without changing the degree of mitochondrial membrane fatty acid unsaturation. Forty percent MetR, differing from 80% MetR, did not inhibit the increase in rat body weight. These changes are very similar to the ones previously found during dietary and protein restriction in rats. We conclude that methionine is the only dietary factor responsible for the decrease in mitochondrial ROS production and oxidative stress, and likely for part of the longevity extension effect, occurring in DR. |
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Authors:
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Pilar Caro; Jose Gomez; Ines Sanchez; Alba Naudi; Victoria Ayala; Monica L?pez-Torres; Reinald Pamplona; Gustavo Barja |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Rejuvenation research Volume: 12 ISSN: 1557-8577 ISO Abbreviation: Rejuvenation Res Publication Date: 2009 Dec |
Date Detail:
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Created Date: 2009-12-31 Completed Date: 2010-03-03 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101213381 Medline TA: Rejuvenation Res Country: United States |
Other Details:
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Languages: eng Pagination: 421-34 Citation Subset: IM |
Affiliation:
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Department of Animal Physiology II, Complutense University of Madrid, Madrid, Spain. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Body Weight / drug effects Brain / metabolism Caloric Restriction DNA, Mitochondrial / metabolism* Diet Electron Transport Electron Transport Complex I / metabolism* Free Radicals / metabolism* Kidney / metabolism Male Methionine / pharmacology* Mitochondria / drug effects, metabolism* Mitochondrial Proteins / metabolism* Oxidative Stress / drug effects* Oxygen Consumption / drug effects Rats Rats, Wistar Reactive Oxygen Species / metabolism |
| Chemical | |
Reg. No./Substance:
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0/DNA, Mitochondrial; 0/Free Radicals; 0/Mitochondrial Proteins; 0/Reactive Oxygen Species; 63-68-3/Methionine; EC 1.6.5.3/Electron Transport Complex I |
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