Cycles of mitochondrial energization driven by the ultradian clock in a continuous culture of Saccharomyces cerevisiae

Lloyd, David; Salgado, L. Eshantha J.; Turner, Marion; Suller, M. T. E.; Murray, Douglas B.

doi:10.1099/00221287-148-11-3715

Cited by 59 publications

(40 citation statements)

References 35 publications

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“…During the reductive phase of the cycle transcript, abundance was enriched with transcripts responsible for respiration, mitochondrial biogenesis, and actin arrangement. This production was compatible with our previous observation that mitochondrial cristae oscillate between orthodox (oxidative phase) and a condensed (reductive phase) state during a respiratory cycle (11). From these data we estimate that the metabolite concentrations peak 100-150°(12-18 min) after the peak in transcriptional activation of the pathway.…”

Section: Resultssupporting

confidence: 79%

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Regulation of yeast oscillatory dynamics

Murray

Beckmann

Kitano

2007

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

137

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: Resultssupporting

confidence: 79%

“…5] for months (4)(5)(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.…”

mentioning

confidence: 99%

Regulation of yeast oscillatory dynamics

Murray

Beckmann

Kitano

2007

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

137

151

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“…2E and (18,19,32,35,41,44). As a consequence, protein diffusion in the mitochondrial matrix may be affected (39,56).…”

Section: Resultsmentioning

confidence: 99%

“…It is well established that changes in mitochondrial metabolism influence mitochondrial shape and matrix configuration (2,18,19,32,41,44) and thus the exchange of metabolites across the inner mitochondrial membrane and diffusion of matrix constituents (32,44,56). Using confocal microscopy and fluorescence correlation spectroscopy (FCS) of human skin fibroblasts expressing enhanced yellow fluorescent protein (EYFP) in the mitochondrial matrix (mitoEYFP), we recently showed that chronic CI inhibition by rotenone increased mitochondrial length and degree of branching and decreased the fraction of moving mitochondria and their velocity (27,30).…”

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confidence: 99%

Inherited complex I deficiency is associated with faster protein diffusion in the matrix of moving mitochondria

Koopman

Distelmaier²,

Hink³

et al. 2008

American Journal of Physiology-Cell Physiology

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Willems PH. Inherited complex I deficiency is associated with faster protein diffusion in the matrix of moving mitochondria. Am J Physiol Cell Physiol 294: C1124-C1132, 2008. First published March 19, 2008 doi:10.1152/ajpcell.00079.2008.-Mitochondria continuously change shape, position, and matrix configuration for optimal metabolite exchange. It is well established that changes in mitochondrial metabolism influence mitochondrial shape and matrix configuration. We demonstrated previously that inhibition of mitochondrial complex I (CI or NADH:ubiquinone oxidoreductase) by rotenone accelerated matrix protein diffusion and decreased the fraction and velocity of moving mitochondria. In the present study, we investigated the relationship between inherited CI deficiency, mitochondrial shape, mobility, and matrix protein diffusion. To this end, we analyzed fibroblasts of two children that represented opposite extremes in a cohort of 16 patients, with respect to their residual CI activity and mitochondrial shape. Fluorescence correlation spectroscopy (FCS) revealed no relationship between residual CI activity, mitochondrial shape, the fraction of moving mitochondria, their velocity, and the rate of matrix-targeted enhanced yellow fluorescent protein (mitoEYFP) diffusion. However, mitochondrial velocity and matrix protein diffusion in moving mitochondria were two to three times higher in patient cells than in control cells. Nocodazole inhibited mitochondrial movement without altering matrix EYFP diffusion, suggesting that both activities are mutually independent. Unexpectedly, electron microscopy analysis revealed no differences in mitochondrial ultrastructure between control and patient cells. It is discussed that the matrix of a moving mitochondrion in the CI-deficient state becomes less dense, allowing faster metabolite diffusion, and that fibroblasts of CI-deficient patients become more glycolytic, allowing a higher mitochondrial velocity.

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“…Oscillation has been shown to occur in extreme metabolic conditions such as ischemia or substance depression in different models such as isolated cardiac mitochondria (6,7), cardiac myocytes (21), neurons (19,28,29), and yeast (13)(14)(15)(16). It has also been known that dissolved oxygen has oscillation in yeast (22).…”

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confidence: 99%

Oscillation of oxygenation in skeletal muscle at rest and in light exercise

Yano

Cs²,

Arimitsu³

et al. 2013

Acta Physiologica Hungarica

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The aim of the present study was to compare the frequency of oxygenation determined in the vastus lateralis by near-infrared spectroscopy (NIRS) in light exercise with that at rest. A subject rested in a recumbent position for 5 min and changed body position to a sitting position on a cycle ergometer for 9 min. Then exercise with low intensity (work rate of 60% of maximal oxygen uptake) was carried out for 30 min. Total hemoglobin and myoglobin (THb/Mb) suddenly decreased after the start of exercise and gradually increased until 6 min. Oxygenated hemoglobin and myoglobin (Hb/MbO2) suddenly decreased and returned to a steady state after the start of exercise. The difference between Hb/MbO2 and THb/Mb showed a sudden decrease and then a steady state. This difference was analyzed by fast Fourier transform. The peak frequencies of the power spectrum density (PSD) were 0.0169 + 0.0076 Hz at rest and 0.0117 + 0.0042 Hz in exercise. The peak frequency of PSD was significantly decreased in exercise. In exercise, the range of frequencies was expanded. It is concluded that there are oscillations at rest as well as in exercise and that the frequency of peak PSD becomes lower in exercise than at rest

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Cycles of mitochondrial energization driven by the ultradian clock in a continuous culture of Saccharomyces cerevisiae

Cited by 59 publications

References 35 publications

Regulation of yeast oscillatory dynamics

Regulation of yeast oscillatory dynamics

Inherited complex I deficiency is associated with faster protein diffusion in the matrix of moving mitochondria

Oscillation of oxygenation in skeletal muscle at rest and in light exercise

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