The stationary phase model of aging in yeast for the study of oxidative stress and age-related neurodegeneration

Chen, Quinghua; Qian, Dali; Keller, Jeffrey N.

doi:10.1007/s10522-004-7379-6

Cited by 57 publications

(60 citation statements)

References 54 publications

(193 reference statements)

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“…Wild-type cells that are grown in synthetic complete minimal medium lose viability after 10 d (our unpublished observations). In contrast, cells that are grown and maintained in stationary phase on rich media can maintain viability for weeks (Sinclair et al, 1998;Chen et al, 2005). We found that there was a rapid decline in the viability of our oye2⌬ cells compared with wild-type cells (Figure 4).…”

Section: C374amentioning

confidence: 82%

Conserved Actin Cysteine Residues Are Oxidative Stress Sensors That Can Regulate Cell Death in Yeast

Farah

Amberg

2007

MBoC

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Actin's functional complexity makes it a likely target of oxidative stress but also places it in a prime position to coordinate the response to oxidative stress. We have previously shown that the NADPH oxidoreductase Oye2p protects the actin cytoskeleton from oxidative stress. Here we demonstrate that the physiological consequence of actin oxidation is to accelerate cell death in yeast. Loss of Oye2p leads to reactive oxygen species accumulation, activation of the oxidative stress response, nuclear fragmentation and DNA degradation, and premature chronological aging of yeast cells. The oye2⌬ phenotype can be completely suppressed by removing the potential for formation of the actin C285-C374 disulfide bond, the likely substrate of the Oye2p enzyme or by treating the cells with the clinically important reductant N-acetylcysteine. Because these two cysteines are coconserved in all actin isoforms, we theorize that we have uncovered a universal mechanism whereby actin helps to coordinate the cellular response to oxidative stress by both sensing and responding to oxidative load.

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Section: C374amentioning

confidence: 82%

Conserved Actin Cysteine Residues Are Oxidative Stress Sensors That Can Regulate Cell Death in Yeast

Farah

Amberg

2007

MBoC

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“…Strikingly, many of the key aspects of yeast aging closely resemble those of mammalian cells, especially postmitotic neurons (for example oxidative stress, decreased proteasome function and the accumulation of somatic mutations) [134][135][136] . The biology of postmitotic cells is profoundly different than that of dividing cells and since in almost all of these diseases it is predominantly postmitotic neurons that are affected, examining yeast models of neurodegenerative disease in the context of nondividing aged cells will be crucial, and perhaps much more directly relevant to the biology of aging neurons [137] . There are 2 types of aging models in yeast: replicative and chronological [138,139] .…”

Section: The Effect Of Aging On Yeast Neurodegenerative Disease Modelsmentioning

confidence: 99%

Beer and Bread to Brains and Beyond: Can Yeast Cells Teach Us about Neurodegenerative Disease?

Gitler

2007

Neurosignals

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For millennia, humans have harnessed the astonishing power of yeast, producing such culinary masterpieces as bread, beer and wine. Therefore, in this new millennium, is it very farfetched to ask if we can also use yeast to unlock some of the modern day mysteries of human disease? Remarkably, these seemingly simple cells possess most of the same basic cellular machinery as the neurons in the brain. We and others have been using the baker’s yeast, Saccharomyces cerevisiae, as a model system to study the mechanisms of devastating neurodegenerative diseases such as Parkinson’s, Huntington’s, Alzheimer’s and amyotrophic lateral sclerosis. While very different in their pathophysiology, they are collectively referred to as protein-misfolding disorders because of the presence of misfolded and aggregated forms of various proteins in the brains of affected individuals. Using yeast genetics and the latest high-throughput screening technologies, we have identified some of the potential causes underpinning these disorders and discovered conserved genes that have proven effective in preventing neuron loss in animal models. Thus, these genes represent new potential drug targets. In this review, I highlight recent work investigating mechanisms of cellular toxicity in a yeast Parkinson’s disease model and discuss how similar approaches are being applied to additional neurodegenerative diseases.

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“…Recent studies have demonstrated that yeast are a useful model with which to study ␣-synuclein toxicity (17)(18)(19), with the previous studies in mitotic yeast contributing to our understanding of what cellular processes are likely important in promoting and inhibiting ␣-synuclein toxicity. Numerous studies have demonstrated that yeast are also useful in studying the biochemistry and regulation of aging in both mitotic and post-mitotic cells (20 -22).…”

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confidence: 99%

α-Synuclein Alters Proteasome Function, Protein Synthesis, and Stationary Phase Viability

Chen

Thorpe

Keller

2005

Journal of Biological Chemistry

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␣-Synuclein appears to play a role in mediating neurotoxicity in a number of neurodegenerative disorders, collectively referred to as synucleinopathies. Most of these disorders are associated with aging and a probable impairment of the proteasome-proteolytic pathway, although the relationship between aging, proteasome inhibition, and ␣-synuclein toxicity has not been fully elucidated. Recent studies suggest that yeast may provide a useful system for studying the biology and toxicity of ␣-synuclein in mitotic cells, recapitulating many features observed in the various synucleinopathy disorders. Additional studies indicate that the stationary phase model of aging in yeast provides a useful system for understanding the biochemistry and regulation of aging in post-mitotic cells. In the present study we examined the effect of wild type and mutant ␣-synuclein (A30P) on multiple aspects of proteasome homeostasis, protein synthesis, as well as the ability of cells to survive stationary phase aging. These data demonstrate that ␣-synuclein alters proteasome composition, impairs proteasome-mediated protein degradation, impairs protein synthesis, and impairs the ability of cells to withstand stationary phase aging. Interestingly, ␣-synuclein had little effect on intracellular proteasome content or protein ubiquitination, and did not increase the vulnerability of cells to a variety of stressors. Together, these data suggest that yeast may be useful for understanding the ability of ␣-synuclein to impair proteasome-mediated protein degradation, as well as for understanding the basis for age-related ␣-synuclein cytotoxicity.

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The stationary phase model of aging in yeast for the study of oxidative stress and age-related neurodegeneration

Cited by 57 publications

References 54 publications

Conserved Actin Cysteine Residues Are Oxidative Stress Sensors That Can Regulate Cell Death in Yeast

Conserved Actin Cysteine Residues Are Oxidative Stress Sensors That Can Regulate Cell Death in Yeast

Beer and Bread to Brains and Beyond: Can Yeast Cells Teach Us about Neurodegenerative Disease?

α-Synuclein Alters Proteasome Function, Protein Synthesis, and Stationary Phase Viability

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