Intracellular Time Keeping: Epigenetic Oscillations Reveal the Functions of an Ultradian Clock

Lloyd, David

doi:10.1007/978-1-4471-1969-2_1

Cited by 29 publications

(17 citation statements)

References 61 publications

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“…This ultradian clock was observed as a temperature-compensated rhythm with a period of about an hour in synchronously dividing cultures of the small soil amoeba, Acanthamoeba castellanii. (11 -13) Similar ultradian clocks were observed in other protists (ciliates and flagellates) (14) and in yeasts. (15) Drosophila melanogaster was shown to have a millisecond clock.…”

Section: Introductionsupporting

confidence: 65%

Redox rhythmicity: clocks at the core of temporal coherence

Lloyd

Murray

2007

BioEssays

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Ultradian rhythms are those that cycle many times in a day and are therefore measured in hours, minutes, seconds or even fractions of a second. In yeasts and protists, a temperature-compensated clock with a period of about an hour (30-90 minutes) provides the time base upon which all central processes are synchronized. A 40-minute clock in yeast times metabolic, respiratory and transcriptional processes, and controls cell division cycle progression. This system has at its core a redox cycle involving NAD(P)H and dithiol-disulfide interconversions. It provides an archetype for biological time keeping on longer time scales (e.g. the daily cycles driven by circadian clocks) and underpins these rhythms, which cannot be understood in isolation. Ultradian rhythms are the foundation upon which the coherent functioning of the organism depends.

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Section: Introductionsupporting

confidence: 65%

Redox rhythmicity: clocks at the core of temporal coherence

Lloyd

Murray

2007

BioEssays

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“…the extramitochondrial events that produce the slow kinetics of transcriptional switching that generate the time-base of the temperaturecompensated ultradian clock Salgado et al, 2002). The continuously monitored system described here for study of ultradian clock outputs in S. cerevisiae is more convenient and amenable than other ultradian systems (Lloyd, 1992) and many circadian systems (Lloyd et al, 1982b ;Lloyd, 1988) where only discrete sampling is possible (Lloyd & Murray, 2000), and where the accumulation of useful data requires more extended time intervals.…”

Section: Lloyd and Othersmentioning

confidence: 99%

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

et al. 2002

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A continuous culture of Saccharomyces cerevisiae IFO 0233, growing with glucose as the major carbon and energy source, shows oscillations of respiration with a period of 48 min. Samples taken at maxima and minima indicate that (i) periodic changes do not occur as a result of carbon depletion, (ii) intrinsic differences in respiratory activity occur in washed organisms and (iii) a respiratory inhibitor accumulates during respiratory oscillations. Plasma membrane and inner mitochondrial membranes generate transmembrane electrochemical potentials ; changes in these can be respectively assessed using anionic or cationic fluorophores. Thus flow cytometric analyses indicated that an oxonol dye [DiBAC 4 (3) ; bis(1,3-dibutylbarbituric acid)trimethine oxonol] was excluded from yeasts to a similar extent (in S98 % of the population) at all stages, showing that the plasma membrane potential was maintained at a steady value. However, uptake of Rhodamine 123 was greatest at that phase characterized by a low respiratory rate. Addition of uncouplers of energy conservation [CCCP (m-chlorocarbonylcyanide phenylhydrazone) or S-13 (5-chloro-3-t-butyl-2-chloro-4 1 -nitrosalicylanilide)] to the continuous cultures increased the respiration, but had only a transient effect on the period of the oscillation. Electron microscopy showed changes in mitochondrial ultrastructure during the respiratory oscillation. At low respiration the cristae were more clearly defined due to swelling of the matrix ; this corresponds to the ' orthodox ' conformation. When respiration was high the mitochondrial configuration was ' condensed '. It has been shown previously that a temperature-compensated ultradian clock operates in S. cerevisiae. It is proposed that mitochondria undergo cycles of energization in response to energetic demands driven by this ultradian clock output.

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“…Rescaled (Hurst) analysis for rat parotid gland cell dry mass in rats fed at 2 h intervals (see Table 2 Lloyd, 1992 ;Rossi & Lippincott, 1992). Ultradian rhythms of some organ functions and organism behaviour have been described since the 1960s (reviewed by Lloyd & Rossi, 1992).…”

Section: Nature Of Intracellular Ultradian Rhythmsmentioning

confidence: 99%

“…The first of these seems unlikely bearing in mind the rather short periods, and high level of variability with chaotic interchange of periods of ultradian rhythms. At present, these rhythms are considered to be '' epigenetic '' (see Lloyd, 1992).…”

Section: Nature Of Intracellular Ultradian Rhythmsmentioning

confidence: 99%

“…In addition to cellular functions, a resemblance of ultradian rhythms to fractals was noted for organ and organism functions (Goldberger & West, 1987 ;Szeto et al, 1990 ; Table 3. Rescaled (Hurst) analysis for rat parotid gland cell dry mass in rats fed at 2 h intervals (see Table 2 Lloyd, 1992 ;Rossi & Lippincott, 1992). Ultradian rhythms of some organ functions and organism behaviour have been described since the 1960s (reviewed by Lloyd & Rossi, 1992).…”

Section: Nature Of Intracellular Ultradian Rhythmsmentioning

confidence: 99%

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Direct cell–cell communication: a new approach derived from recent data on the nature and self-organisation of ultradian (circahoralian) intracellular rhythms

Brodsky

2005

Biol. Rev.

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Recent data concerning ultradian (circahoralian) intracellular rhythms are used to assess the biochemical mechanisms of direct cell-cell communication. New results and theoretical considerations suggest a fractal nature of ultradian rhythms and their self-organisation. The fundamental and innate nature of these rhythms relates to their self-similarity at different levels of cell and tissue organisation. They can be detected in cell-free systems as well as in cells and organs in vivo. Such rhythms are a means of finding an optimal state of cell function rather than achieving a state of absolute stability. As a consequence, oscillations, being irregular and numerous by the set of periods, are resilient to functional overload and injury. Recent data on the maintenance of their fractal structure and, especially on the selection of optimal periods are discussed. The positive role of chaotic dynamics is stressed. The ultradian rhythm of protein synthesis in hepatocytes in vitro was used as a marker of direct cell-cell communication. The system demonstrates cell cooperation and synchronisation throughout the cell population, and suggests that the ultradian rhythms are self-organised. These observations also led to the detection of mechanisms of direct cell-cell communication in which extracellular factors have an essential role. Experimental evidence indicated the involvement of gangliosides and/or catecholamines in this large-scale synchronisation of protein synthesis. The response of all, or a major part, of the cell population is important; after the initial trigger effect, a periodic pattern is retained for some time. The influence of Ca2+-dependent protein kinases on protein phosphorylation can be a final step in the phase modulation of rhythms during cell-cell synchronisation. The intercellular medium plays an important role in self-synchronisation of ultradian rhythms between individual cells. Low cooperative activity of hepatocytes of old rats resulted from altered composition of the intercellular medium rather than direct effects of animal and cellular ageing. Similarly, in the whole body, changes in levels of gangliosides and catecholamines in the blood serum, a natural intercellular medium, can be critical events in age-dependent changes of the serum and accordingly cell-cell synchronisation. Hepatocytes of old rats exhibit some of the properties of young cells following an increase in blood serum ganglioside level, as well as, in in vitro conditions, after the addition of gangliosides to the culture medium. Together with data on ultradian functional and metabolic rhythms, all the material reviewed here allows us to propose a mechanism of direct cell-cell cooperation via the medium in which the cells exist, that supplements the nervous and hormonal central regulation of organ functions. Ultradian intracellular rhythms may thus provide a finer framework within which the integrated dynamics of respiration, heart rate, brain activity, and even behavioural patterns, are brought to an optimal functional pattern. I...

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Intracellular Time Keeping: Epigenetic Oscillations Reveal the Functions of an Ultradian Clock

Cited by 29 publications

References 61 publications

Redox rhythmicity: clocks at the core of temporal coherence

Redox rhythmicity: clocks at the core of temporal coherence

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

Direct cell–cell communication: a new approach derived from recent data on the nature and self-organisation of ultradian (circahoralian) intracellular rhythms

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