Cell density dependence of oscillatory metabolism

Aldridge, Julie; Pye, Erica

doi:10.1038/259670a0

Cited by 96 publications

(67 citation statements)

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“…These findings have implications for our understanding of the mixing experiment and of the loss of oscillations observed at low cell densities (S. De Monte, F. d'Ovidio, S.D., and P.G.S., unpublished data) (24). The transient loss of macroscopic oscillations seen in the mixing experiment is not simply due to averaging of two oscillatory signals 180°out of phase.…”

Section: Discussionmentioning

confidence: 85%

Quantitative characterization of cell synchronization in yeast

Danø

Sørensen²

2007

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

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Metabolic oscillations in baker's yeast serve as a model system for synchronization of biochemical oscillations. Despite widespread interest, the complexity of the phenomenon has been an obstacle for a quantitative understanding of the cell synchronization process. In particular, when two yeast cell populations oscillating 180°out of phase are mixed, it appears as if the synchronization dynamics is too fast to be explained. We have probed the synchronization dynamics by forcing experiments in an open-flow reactor, and we find that acetaldehyde has a very strong synchronization effect that can account quantitatively for the classical mixing experiment. The fast synchronization dynamics is explained by a general synchronization mechanism, which is dominated by a fast amplitude response as opposed to the expected slow phase change. We also show that glucose can mediate this kind of synchronization, provided that the glucose transporter is not saturated. This makes the phenomenon potentially relevant for a broad range of cell types. . A manifest demonstration of this phenomenon occurs when two suspensions oscillating 180°out of phase are mixed. Just after mixing, the macroscopic oscillations disappear momentarily, but the two subpopulations synchronize within 5 min (i.e., Ͻ10 times the period of the oscillations) and the macroscopic oscillations reappear with full amplitude (3-5). This indicates active in-phase synchronization. It is believed that the synchronization is mediated by simple metabolites related to glycolysis (1,4,5), and as such it is an example of cell-cell communication that does not depend on any highly specialized signaling molecules or receptors. A similar synchronization mechanism could be operative in any oscillatory cell type, possibly through other metabolic signaling channels. Therefore, the understanding of the mechanism for glycolytic cell synchronization in yeast is important for the general understanding of cellular dynamics and interactions. Acetaldehyde (Aca) has been proposed as mediator of the synchronization (5). If this is the true mechanism of the phenomenon, then this understanding should allow us to explain it not only qualitatively but also quantitatively correct. It has been questioned whether the amount of Aca produced by the yeast cells is enough to cause synchronization (1), and several attempts have been made to account quantitatively for the synchronization process by using mathematical models based on biochemical descriptions (6-8). None of these have, however, been successful in explaining all experimental facts. In all cases, the synchronization process is one order of magnitude too slow, and in some cases the models even predict out-of-phase synchronization instead of the inphase synchronization seen experimentally.A necessary condition for a chemical species to act as a synchronizer is that it can penetrate the cell membrane, and that an instantaneous change in its concentration will influence the oscillations and give rise to an amplitude or phase change. Many differ...

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Section: Discussionmentioning

confidence: 85%

Quantitative characterization of cell synchronization in yeast

Danø

Sørensen²

2007

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

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“…Synthetic oligonucleotides for 5¢ and 3¢ primers, 3 and 4 for TDH1, Table 1. List of synthetic oligonucleotides used for primers (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13) or probes (14,15) in this experiment.…”

Section: Preparation Of Tdh-deleted Mutantsmentioning

confidence: 99%

“…This loss of biological rhythms in the TDH1-deleted mutant was rescued by the expression of TDH1 but not of TDH2 or TDH3 under the control of the TDH1 promoter. Thus, we hypothesized that Gts1p plays a role in the regulation of metabolic oscillation by interacting with the TDH1 product, GAPDH1, in yeast.Keywords: continuous culture; glyceraldehyde-3-phosphate dehydrogenase; Gts1p; metabolic oscillation; yeast.Ultradian (cycles with a period shorter than 24 h) oscillations of the glycolytic pathway were induced after addition of glucose by inhibiting mitochondrial respiration with cyanide in cell suspensions [1][2][3] or cell extracts [4] of yeast with a periodicity of 1-2 min as monitored by measuring the level of NAD(P)H (reviewed in [5]). The glycolytic pathway has been shown to be an autogenous oscillator under extreme nonequilibrium conditions of energy in dissipative structures, which theoretically include all living organisms [5][6][7].…”

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confidence: 99%

“…Ultradian (cycles with a period shorter than 24 h) oscillations of the glycolytic pathway were induced after addition of glucose by inhibiting mitochondrial respiration with cyanide in cell suspensions [1][2][3] or cell extracts [4] of yeast with a periodicity of 1-2 min as monitored by measuring the level of NAD(P)H (reviewed in [5]). The glycolytic pathway has been shown to be an autogenous oscillator under extreme nonequilibrium conditions of energy in dissipative structures, which theoretically include all living organisms [5][6][7].…”

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confidence: 99%

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Interaction of the GTS1 gene product with glyceraldehyde‐ 3‐phosphate dehydrogenase 1 required for the maintenance of the metabolic oscillations of the yeast Saccharomyces cerevisiae

Liu

Wang

Mitsui

et al. 2002

European Journal of Biochemistry

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We previously reported that GTS1 is involved in regulating ultradian oscillations of the glycolytic pathway induced by cyanide in cell suspensions as well as oscillations of energy metabolism in aerobic continuous cultures. Here, we screened a yeast cDNA library for proteins that bind to Gts1p using the yeast two-hybrid system and cloned multiple TDH cDNAs encoding the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH). We found that the zinc-finger and dimerization sites of Gts1p were required for full ability to bind GAPDH, and Gts1ps mutated at these sites lost the ability to regulate both aerobic and unaerobic ultradian oscillations of energy metabolism.Of the three TDH genes, only TDH1 fluctuated at the mRNA level in continuous culture and its deletion resulted in the disappearance of the oscillation without any affect on growth rate. This loss of biological rhythms in the TDH1-deleted mutant was rescued by the expression of TDH1 but not of TDH2 or TDH3 under the control of the TDH1 promoter. Thus, we hypothesized that Gts1p plays a role in the regulation of metabolic oscillation by interacting with the TDH1 product, GAPDH1, in yeast.Keywords: continuous culture; glyceraldehyde-3-phosphate dehydrogenase; Gts1p; metabolic oscillation; yeast.Ultradian (cycles with a period shorter than 24 h) oscillations of the glycolytic pathway were induced after addition of glucose by inhibiting mitochondrial respiration with cyanide in cell suspensions [1][2][3] or cell extracts [4] of yeast with a periodicity of 1-2 min as monitored by measuring the level of NAD(P)H (reviewed in [5]). The glycolytic pathway has been shown to be an autogenous oscillator under extreme nonequilibrium conditions of energy in dissipative structures, which theoretically include all living organisms [5][6][7]. The pathway oscillates under the primary control of phosphofructokinase [8,9], transferring energy from glucose to NADH, which acts as the feed-forward activator, and then from NADH to ATP, which acts as the feedback inhibitor. After ATP as an inhibitor has been consumed, glucose again begins to enter the glycolytic pathway. Yeast cells also exhibit sustained ultradian oscillations of energy metabolism, with a periodicity of 4 h in continuous (chemostat) culture under aerobic conditions in an open system using a bioreactor [10][11][12][13]. (Hereafter, aerobic oscillation will be referred to as energy metabolism or metabolic oscillation in distinction from cyanide-induced glycolytic oscillation.) Energy-metabolism oscillations, which arise spontaneously under conditions of high cell density ( 5 · 10 8 cellsAEmL )1 ) [14], are detectable as a periodic change in the factors involved in energy metabolism such as dissolved oxygen (DO) levels, CO 2 production, glucose and ethanol concentrations, and amounts of storage carbohydrates [10][11][12][13]. DO oscillation is caused by the periodic change between respiratory and respiratory-fermentative phases, in which oxygen demands are relatively high and low, respectively. Although ...

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“…[18][19][20] In biology, limit cycle systems are of particular interest, since some of them provide the mechanisms for various biological clocks, including the one governing the cell cycle. 21,22 Metabolic oscillations occur in yeast extracts, in populations of yeast cells (see, for example, refs [23][24][25][26][27][28][29][30][31][32], and in photosynthesis. 33 There is a growing interest in the yeast oscillations because they involve active cell-cell synchronization.…”

Section: Introductionmentioning

confidence: 99%

Control Analysis of Periodic Phenomena in Biological Systems

1997

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Control analysis of periodic phenomena in biological systemsKholodenko, B.N.; Demin, O.V.; Westerhoff, H.V. General rightsIt is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulationsIf you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: http://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. Download date: 10 May 2018 Control Analysis of Periodic Phenomena in Biological SystemsBoris N. Kholodenko,* , † Oleg V. Demin, ‡ and Hans V. Westerhoff §,| Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson UniVersity, 1020 Locust Street, Philadelphia, PennsylVania 19107, A.N. Belozersky Institute of Physico-Chemical Biology, Moscow State UniVersity, 119899 Moscow, Russia, Department of Microbial Physiology, Free UniVersity, De Boelelaan 1087, NL-1081 HV Amsterdam, The Netherlands, and E. C. Slater Institute, Biocentrum, UniVersity of Amsterdam, Plantage Muidergracht 12, The Netherlands ReceiVed: July 31, 1996 In Final Form: January 7, 1997 X Principles of the control and regulation of steady-state metabolic systems have been identified in terms of the concepts and laws of metabolic control analysis (MCA). With respect to the control of periodic phenomena MCA has not been equally successful. This paper shows why in case of autonomous (self-sustained) oscillations for the concentrations and reaction rates, time-dependent control coefficients are not useful to characterize the system: they are neither constant nor periodic and diverge as time progresses. This is because a controlling parameter tends to change the frequency and causes a phase shift that continuously increases with time. This recognition is important in the extension of MCA for periodic phenomena. For oscillations that are enforced with an externally determined frequency, the time-dependent control coefficients over metabolite concentration and fluxes (reaction rates) are shown to have a complete meaning. Two such time-dependent control coefficients are defined for forced oscillations. One, the so-called periodic control coefficient, measures how the stationary periodic movement depends on the activities of one of the enzymes. The other, the socalled transient control coefficient, measures the control over the transition of the system between two stationary oscillations, as induced by a change in one of the enzyme activities. For forced oscillations, the two control coefficients become equal as time tends to infinity. N...

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Cell density dependence of oscillatory metabolism

Cited by 96 publications

References 7 publications

Quantitative characterization of cell synchronization in yeast

Quantitative characterization of cell synchronization in yeast

Interaction of the GTS1 gene product with glyceraldehyde‐ 3‐phosphate dehydrogenase 1 required for the maintenance of the metabolic oscillations of the yeast Saccharomyces cerevisiae

Control Analysis of Periodic Phenomena in Biological Systems

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