GLR1Plays an Essential Role in the Homeodynamics of Glutathione and the Regulation of H2S Production during Respiratory Oscillation ofSaccharomyces cerevisiae

Sohn, Ho-Yong; Kum, Eun-Joo; Kwon, Gi-Seok; Jin, Ingnyol; Adams, Claire A.; Kuriyama, Hiroshi

doi:10.1271/bbb.69.2450

Cited by 12 publications

(8 citation statements)

References 18 publications

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“…The activation of GCN4 translation was not the result of amino acids in the feed media becoming limited because extracellular amino acids were always below the limits of detection, and ammonia was always available for biosynthesis (25). Furthermore, addition of glutamate, cysteine, and threonine causes dose-dependent inhibition of respiration and growth (7,26,27), which is the opposite of what may be expected if the cell were limited by amino acids. In addition, the respiratory oscillation was sensitive to low concentrations of rapamycin, resulting in a switch to reductive phase for 60 h (Fig.…”

Section: Resultsmentioning

confidence: 99%

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Regulation of yeast oscillatory dynamics

Murray

Beckmann

Kitano

2007

Proc. Natl. Acad. Sci. U.S.A.

136

151

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When yeast cells are grown continuously at high cell density, a respiratory oscillation percolates throughout the population. Many essential cellular functions have been shown to be separated temporally during each cycle; however, the regulatory mechanisms involved in oscillatory dynamics remain to be elucidated. Through GC-MS analysis we found that the majority of metabolites show oscillatory dynamics, with 70% of the identified metabolite concentrations peaking in conjunction with NAD(P)H. Through statistical analyses of microarray data, we identified that biosynthetic events have a defined order, and this program is initiated when respiration rates are increasing. We then combined metabolic, transcriptional data and statistical analyses of transcription factor activity, identified the top oscillatory parameters, and filtered a large-scale yeast interaction network according to these parameters. The analyses and controlled experimental perturbation provided evidence that a transcriptional complex formed part of the timing circuit for biosynthetic, reductive, and cell cycle programs in the cell. This circuitry does not act in isolation because both have strong translational, proteomic, and metabolic regulatory mechanisms. Our data lead us to conclude that the regulation of the respiratory oscillation revolves around coupled subgraphs containing large numbers of proteins and metabolites, with a potential to oscillate, and no definable hierarchy, i.e., heterarchical control. metabolic regulation ͉ respiratory oscillation ͉ temporal structure ͉ transcriptional regulation ͉ self-organization A s we obtain a greater understanding of systems dynamics, it is becoming apparent that biological oscillators play critical roles in the organization of physiology in all time scales, ranging from milliseconds to years (1, 2). At the end of yeast growth in batch culture, there is series of cycles in respiratory activity that occur before the culture entering stationary phase (3). When continuous culture is initiated, the culture can be maintained in this oscillatory state [40 min to 5 h; see supporting information (SI) Fig. 5] for months (4-6). These dynamics result in the temporal separation of many essential cellular functions, including redox biochemistry (7,8), transcription (9, 10), energetics (11), chromosome cycle (1), and mitochondrial function (5). Although respiration is always active, the cellular redox state cycles between an oxidative phase and reductive phase. It is known that at least two redox active compounds, acetaldehyde and H 2 S, mediate cell-cell communication (12), but little is known regarding how synchrony is generated within the cell and how the network is regulated.A major problem in elucidating the oscillatory mechanism is the extent to which the cellular network is entrained, i.e., in a system where the majority of parameters oscillate how does one pull out core mechanisms. Fortunately, Saccharomyces cerevisiae has been used extensively as a proving ground for many of the new low-and high-throughpu...

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Section: Resultsmentioning

confidence: 99%

“…The metabolite data set used previous work (5,7,12,21,22,25,27,28,37,38), and GC-MS analyses (SI Methods) of intracellular metabolites were used to construct the metabolite data set. All Western blots were carried out according to the manufacturer's instructions (Atto, Bunkyo-ku, Tokyo, Japan).…”

Section: Methodsmentioning

confidence: 99%

Regulation of yeast oscillatory dynamics

Murray

Beckmann

Kitano

2007

Proc. Natl. Acad. Sci. U.S.A.

136

151

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“…All data shown represent data sets from at least 3 independent sets of analyses period \24 h) [28][29][30]. These oscillations are associated with concerted transcriptomic and metabolomic changes [31][32][33], and are susceptible to particular perturbations, such as altered levels of glutathione [74][75][76]. Indeed, rhythm-dependent oscillations in cellular levels of reducedglutathione (GSH) have recently been shown to underpin the variable Cd resistances of individual yeast cells [30].…”

Section: Cadmium Induces Mitochondrial Membrane Hyperpolarization Andmentioning

confidence: 99%

Cadmium induces a heterogeneous and caspase-dependent apoptotic response in Saccharomyces cerevisiae

2008

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The toxic metal cadmium is linked to a series of degenerative disorders in humans, in which Cd-induced programmed cell death (apoptosis) may play a role. The yeast, Saccharomyces cerevisiae, provides a valuable model for elucidating apoptosis mechanisms, and this study extends that capability to Cd-induced apoptosis. We demonstrate that S. cerevisiae undergoes a glucose-dependent, programmed cell death in response to low cadmium concentrations, which is initiated within the first hour of Cd exposure. The response was associated with induction of the yeast caspase, Yca1p, and was abolished in a yca1Delta mutant. Cadmium-dependent apoptosis was also suppressed in a gsh1Delta mutant, indicating a requirement for glutathione. Other apoptotic markers, including sub-G(1) DNA fragmentation and hyper-polarization of mitochondrial membranes, were also evident among Cd-exposed cells. These responses were not distributed uniformly throughout the cell population, but were restricted to a subset of cells. This apoptotic subpopulation also exhibited markedly elevated levels of intracellular reactive oxygen species (ROS). The heightened ROS levels alone were not sufficient to induce apoptosis. These findings highlight several new perspectives to the mechanism of Cd-dependent apoptosis and its phenotypic heterogeneity, while opening up future analyses to the power of the yeast model system.

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“…During LOC, homocysteine is modified by cystathionine β‐synthase (Cys4) to generate GSH and H 2 S. This branch is important for cycling and cells deficient in CYS4 do not undergo YROs (Murray, Engelen, Lloyd, & Kuriyama, ; Tu et al., ). The ratio of reduced to oxidised glutathione (GSH:GSSG) cycles as a function of the YRO (Sohn et al., ). Altering this ratio by pulse addition of either form, or by inhibition or deletion of glutathione reductase, the enzyme that catalyses interconversion of the two forms, perturbs or abolishes YROs (Murray et al., ; Sohn et al., ).…”

Section: Characteristics Of Metabolic Rhythmsmentioning

confidence: 99%

“…The ratio of reduced to oxidised glutathione (GSH:GSSG) cycles as a function of the YRO (Sohn et al., ). Altering this ratio by pulse addition of either form, or by inhibition or deletion of glutathione reductase, the enzyme that catalyses interconversion of the two forms, perturbs or abolishes YROs (Murray et al., ; Sohn et al., ). Sulphur‐based regulation of redox state also underpins conidiation rhythms in Neurospora (Onai & Nakashima, ).…”

Section: Characteristics Of Metabolic Rhythmsmentioning

confidence: 99%

Metabolic rhythms: A framework for coordinating cellular function

Causton

2018

Eur J of Neuroscience

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Circadian clocks are widespread among eukaryotes and generally involve feedback loops coupled with metabolic processes and redox balance. The organising power of these oscillations has not only allowed organisms to anticipate day–night cycles, but also acts to temporally compartmentalise otherwise incompatible processes, enhance metabolic efficiency, make the system more robust to noise and propagate signals among cells. While daily rhythms and the function of the circadian transcription‐translation loop have been the subject of extensive research over the past four decades, cycles of shorter period and respiratory oscillations, with which they are intertwined, have received less attention. Here, we describe features of yeast respiratory oscillations, which share many features with daily and 12 hr cellular oscillations in animal cells. This relatively simple system enables the analysis of dynamic rhythmic changes in metabolism, independent of cellular oscillations that are a product of the circadian transcription‐translation feedback loop. Knowledge gained from studying ultradian oscillations in yeast will lead to a better understanding of the basic mechanistic principles and evolutionary origins of oscillatory behaviour among eukaryotes.

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GLR1Plays an Essential Role in the Homeodynamics of Glutathione and the Regulation of H₂S Production during Respiratory Oscillation ofSaccharomyces cerevisiae

Cited by 12 publications

References 18 publications

Regulation of yeast oscillatory dynamics

Regulation of yeast oscillatory dynamics

Cadmium induces a heterogeneous and caspase-dependent apoptotic response in Saccharomyces cerevisiae

Metabolic rhythms: A framework for coordinating cellular function

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