Identification of potential calorie restriction-mimicking yeast mutants with increased mitochondrial respiratory chain and nitric oxide levels

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

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article number673185
JournalJournal of Aging Research
Volume2011
DOIs
StatePublished - 2011

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Electron Transport
Nitric Oxide
Yeasts
Respiration
S-Nitrosoglutathione
Nitric Oxide Donors
Mitochondrial Proteins
Electron Transport Complex IV
Saccharomyces cerevisiae
Mitochondria
Oxidoreductases
Proteins

ASJC Scopus subject areas

  • Geriatrics and Gerontology

Cite this

Identification of potential calorie restriction-mimicking yeast mutants with increased mitochondrial respiratory chain and nitric oxide levels. / Li, Bin; Skinner, Craig; Castello, Pablo R.; Kato, Michiko; Easlon, Erin; Xie, Li; Li, Tianlin; Lu, Shu Ping; Wang, Chen; Tsang, Felicia; Poyton, Robert O.; Lin, Su Ju.

In: Journal of Aging Research, Vol. 2011, 673185, 2011.

Research output: Contribution to journalArticle

Li, B, Skinner, C, Castello, PR, Kato, M, Easlon, E, Xie, L, Li, T, Lu, SP, Wang, C, Tsang, F, Poyton, RO & Lin, SJ 2011, 'Identification of potential calorie restriction-mimicking yeast mutants with increased mitochondrial respiratory chain and nitric oxide levels', Journal of Aging Research, vol. 2011, 673185. https://doi.org/10.4061/2011/673185
Li, Bin ; Skinner, Craig ; Castello, Pablo R. ; Kato, Michiko ; Easlon, Erin ; Xie, Li ; Li, Tianlin ; Lu, Shu Ping ; Wang, Chen ; Tsang, Felicia ; Poyton, Robert O. ; Lin, Su Ju. / Identification of potential calorie restriction-mimicking yeast mutants with increased mitochondrial respiratory chain and nitric oxide levels. In: Journal of Aging Research. 2011 ; Vol. 2011.
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abstract = "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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AU - Li, Bin

AU - Skinner, Craig

AU - Castello, Pablo R.

AU - Kato, Michiko

AU - Easlon, Erin

AU - Xie, Li

AU - Li, Tianlin

AU - Lu, Shu Ping

AU - Wang, Chen

AU - Tsang, Felicia

AU - Poyton, Robert O.

AU - Lin, Su Ju

PY - 2011

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N2 - 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.

AB - 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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