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Tuesday 25 June 11:30

Phosphofructokinase controls the acetaldehyde induced phase shift in isolated yeast glycolytic oscillators.

Journal article
Authors David van Niekerk
Anna-Karin Gustavsson
M Mojica-Benavides
Caroline B. Adiels
Mattias Goksör
Jacky L Snoep
Published in The Biochemical journal
Volume 476
Issue 2
Pages 353-363
ISSN 1470-8728
Publication year 2019
Published at Department of Physics (GU)
Pages 353-363
Language en
Links dx.doi.org/10.1042/BCJ20180757
www.ncbi.nlm.nih.gov/entrez/query.f...
Subject categories Cell Biology, Molecular biophysics, Biophysics, Kinetics

Abstract

The response of oscillatory systems to external perturbations is crucial for emergent properties such as synchronization and phase locking, and can be quantified in a phase response curve. In individual, oscillating yeast cells, we characterized experimentally the phase response of glycolytic oscillations for external acetaldehyde pulses, and followed the transduction of the perturbation through the system. Subsequently, we analyzed the control of the relevant system components in a detailed mechanistic model. The observed responses are interpreted in terms of the functional coupling and regulation in the reaction network. We find that our model quantitatively predicts the phase dependent phase shift observed in the experimental data. The phase shift is in agreement with an adaptation leading to synchronization with an external signal. Our model analysis establishes that phosphofructokinase plays a key role in the phase shift dynamics as shown in the phase response curve, and adaptation time to external perturbations. Specific mechanism-based interventions, made possible through such analyses of detailed models, can improve upon standard trial and error methods, e.g. melatonin supplementation to overcome jet-lag, which are error prone, specifically, since the effects are phase and dose dependent.

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