Cargando…

A Robust Model for Circadian Redox Oscillations

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 mec...

Descripción completa

Detalles Bibliográficos
Autores principales: del Olmo, Marta, Kramer, Achim, Herzel, Hanspeter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6539027/
https://www.ncbi.nlm.nih.gov/pubmed/31086108
http://dx.doi.org/10.3390/ijms20092368
_version_ 1783422287563718656
author del Olmo, Marta
Kramer, Achim
Herzel, Hanspeter
author_facet del Olmo, Marta
Kramer, Achim
Herzel, Hanspeter
author_sort del Olmo, Marta
collection PubMed
description 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.
format Online
Article
Text
id pubmed-6539027
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-65390272019-06-04 A Robust Model for Circadian Redox Oscillations del Olmo, Marta Kramer, Achim Herzel, Hanspeter Int J Mol Sci Article 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. MDPI 2019-05-13 /pmc/articles/PMC6539027/ /pubmed/31086108 http://dx.doi.org/10.3390/ijms20092368 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
del Olmo, Marta
Kramer, Achim
Herzel, Hanspeter
A Robust Model for Circadian Redox Oscillations
title A Robust Model for Circadian Redox Oscillations
title_full A Robust Model for Circadian Redox Oscillations
title_fullStr A Robust Model for Circadian Redox Oscillations
title_full_unstemmed A Robust Model for Circadian Redox Oscillations
title_short A Robust Model for Circadian Redox Oscillations
title_sort robust model for circadian redox oscillations
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6539027/
https://www.ncbi.nlm.nih.gov/pubmed/31086108
http://dx.doi.org/10.3390/ijms20092368
work_keys_str_mv AT delolmomarta arobustmodelforcircadianredoxoscillations
AT kramerachim arobustmodelforcircadianredoxoscillations
AT herzelhanspeter arobustmodelforcircadianredoxoscillations
AT delolmomarta robustmodelforcircadianredoxoscillations
AT kramerachim robustmodelforcircadianredoxoscillations
AT herzelhanspeter robustmodelforcircadianredoxoscillations