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A Robust Model for Circadian Redox Oscillations

1
Institute for Theoretical Biology, Charité and Humboldt-Universität zu Berlin, 10115 Berlin, Germany
2
Laboratory of Chronobiology, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(9), 2368; https://doi.org/10.3390/ijms20092368
Received: 26 March 2019 / Revised: 8 May 2019 / Accepted: 8 May 2019 / Published: 13 May 2019
(This article belongs to the Special Issue Circadian Rhythms: Molecular and Physiological Mechanisms)
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Abstract

The circadian clock is an endogenous oscillator that controls daily rhythms in metabolism, physiology, and behavior. Although the timekeeping components differ among species, a common design principle is a transcription-translation negative feedback loop. However, it is becoming clear that other mechanisms can contribute to the generation of 24 h rhythms. Peroxiredoxins (Prxs) exhibit 24 h rhythms in their redox state in all kingdoms of life. In mammalian adrenal gland, heart and brown adipose tissue, such rhythms are generated as a result of an inactivating hyperoxidation reaction that is reduced by coordinated import of sulfiredoxin (Srx) into the mitochondria. However, a quantitative description of the Prx/Srx oscillating system is still missing. We investigate the basic principles that generate mitochondrial Prx/Srx rhythms using computational modeling. We observe that the previously described delay in mitochondrial Srx import, in combination with an appropriate separation of fast and slow reactions, is sufficient to generate robust self-sustained relaxation-like oscillations. We find that our conceptual model can be regarded as a series of three consecutive phases and two temporal switches, highlighting the importance of delayed negative feedback and switches in the generation of oscillations. View Full-Text
Keywords: redox; oscillations; mathematical modeling; negative feedback; fast vs. slow reactions; phases; switches redox; oscillations; mathematical modeling; negative feedback; fast vs. slow reactions; phases; switches
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del Olmo, M.; Kramer, A.; Herzel, H. A Robust Model for Circadian Redox Oscillations. Int. J. Mol. Sci. 2019, 20, 2368.

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