Identification of Potential Calorie Restriction-Mimicking Yeast Mutants with Increased Mitochondrial Respiratory Chain and Nitric Oxide Levels

Calorie restriction (CR) induces a metabolic shift towards mitochondrial respiration; however, molecular mechanisms underlying CR remain unclear. Recent studies suggest that CR-induced mitochondrial activity is associated with nitric oxide (NO) production. To understand the role of mitochondria in C...

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Main Authors: Bin Li, Craig Skinner, Pablo R. Castello, Michiko Kato, Erin Easlon, Li Xie, Tianlin Li, Shu-Ping Lu, Chen Wang, Felicia Tsang, Robert O. Poyton, Su-Ju Lin
Format: Article
Language:English
Published: Wiley 2011-01-01
Series:Journal of Aging Research
Online Access:http://dx.doi.org/10.4061/2011/673185
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author Bin Li
Craig Skinner
Pablo R. Castello
Michiko Kato
Erin Easlon
Li Xie
Tianlin Li
Shu-Ping Lu
Chen Wang
Felicia Tsang
Robert O. Poyton
Su-Ju Lin
author_facet Bin Li
Craig Skinner
Pablo R. Castello
Michiko Kato
Erin Easlon
Li Xie
Tianlin Li
Shu-Ping Lu
Chen Wang
Felicia Tsang
Robert O. Poyton
Su-Ju Lin
author_sort Bin Li
collection DOAJ
description Calorie restriction (CR) induces a metabolic shift towards mitochondrial respiration; however, molecular mechanisms underlying CR remain unclear. Recent studies suggest that CR-induced mitochondrial activity is associated with nitric oxide (NO) production. To understand the role of mitochondria in CR, we identify and study Saccharomyces cerevisiae mutants with increased NO levels as potential CR mimics. Analysis of the top 17 mutants demonstrates a correlation between increased NO, mitochondrial respiration, and longevity. Interestingly, treating yeast with NO donors such as GSNO (S-nitrosoglutathione) is sufficient to partially mimic CR to extend lifespan. CR-increased NO is largely dependent on mitochondrial electron transport and cytochrome c oxidase (COX). Although COX normally produces NO under hypoxic conditions, CR-treated yeast cells are able to produce NO under normoxic conditions. Our results suggest that CR may derepress some hypoxic genes for mitochondrial proteins that function to promote the production of NO and the extension of lifespan.
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publisher Wiley
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series Journal of Aging Research
spelling doaj-art-3dbf67eb30674bb9a29e17462e7139002025-02-03T06:11:31ZengWileyJournal of Aging Research2090-22122011-01-01201110.4061/2011/673185673185Identification of Potential Calorie Restriction-Mimicking Yeast Mutants with Increased Mitochondrial Respiratory Chain and Nitric Oxide LevelsBin Li0Craig Skinner1Pablo R. Castello2Michiko Kato3Erin Easlon4Li Xie5Tianlin Li6Shu-Ping Lu7Chen Wang8Felicia Tsang9Robert O. Poyton10Su-Ju Lin11Department of Microbiology, College of Biological Sciences, University of California at Davis, Davis, CA 95616, USADepartment of Microbiology, College of Biological Sciences, University of California at Davis, Davis, CA 95616, USAThe Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, CO 80309, USADepartment of Microbiology, College of Biological Sciences, University of California at Davis, Davis, CA 95616, USADepartment of Microbiology, College of Biological Sciences, University of California at Davis, Davis, CA 95616, USADepartment of Microbiology, College of Biological Sciences, University of California at Davis, Davis, CA 95616, USADepartment of Microbiology, College of Biological Sciences, University of California at Davis, Davis, CA 95616, USADepartment of Microbiology, College of Biological Sciences, University of California at Davis, Davis, CA 95616, USADepartment of Microbiology, College of Biological Sciences, University of California at Davis, Davis, CA 95616, USADepartment of Microbiology, College of Biological Sciences, University of California at Davis, Davis, CA 95616, USAThe Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, CO 80309, USADepartment of Microbiology, College of Biological Sciences, University of California at Davis, Davis, CA 95616, USACalorie restriction (CR) induces a metabolic shift towards mitochondrial respiration; however, molecular mechanisms underlying CR remain unclear. Recent studies suggest that CR-induced mitochondrial activity is associated with nitric oxide (NO) production. To understand the role of mitochondria in CR, we identify and study Saccharomyces cerevisiae mutants with increased NO levels as potential CR mimics. Analysis of the top 17 mutants demonstrates a correlation between increased NO, mitochondrial respiration, and longevity. Interestingly, treating yeast with NO donors such as GSNO (S-nitrosoglutathione) is sufficient to partially mimic CR to extend lifespan. CR-increased NO is largely dependent on mitochondrial electron transport and cytochrome c oxidase (COX). Although COX normally produces NO under hypoxic conditions, CR-treated yeast cells are able to produce NO under normoxic conditions. Our results suggest that CR may derepress some hypoxic genes for mitochondrial proteins that function to promote the production of NO and the extension of lifespan.http://dx.doi.org/10.4061/2011/673185
spellingShingle Bin Li
Craig Skinner
Pablo R. Castello
Michiko Kato
Erin Easlon
Li Xie
Tianlin Li
Shu-Ping Lu
Chen Wang
Felicia Tsang
Robert O. Poyton
Su-Ju Lin
Identification of Potential Calorie Restriction-Mimicking Yeast Mutants with Increased Mitochondrial Respiratory Chain and Nitric Oxide Levels
Journal of Aging Research
title Identification of Potential Calorie Restriction-Mimicking Yeast Mutants with Increased Mitochondrial Respiratory Chain and Nitric Oxide Levels
title_full Identification of Potential Calorie Restriction-Mimicking Yeast Mutants with Increased Mitochondrial Respiratory Chain and Nitric Oxide Levels
title_fullStr Identification of Potential Calorie Restriction-Mimicking Yeast Mutants with Increased Mitochondrial Respiratory Chain and Nitric Oxide Levels
title_full_unstemmed Identification of Potential Calorie Restriction-Mimicking Yeast Mutants with Increased Mitochondrial Respiratory Chain and Nitric Oxide Levels
title_short Identification of Potential Calorie Restriction-Mimicking Yeast Mutants with Increased Mitochondrial Respiratory Chain and Nitric Oxide Levels
title_sort identification of potential calorie restriction mimicking yeast mutants with increased mitochondrial respiratory chain and nitric oxide levels
url http://dx.doi.org/10.4061/2011/673185
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