Abstract

Both circadian rhythm and the production of reactive oxygen species (ROS) are fundamental features of aerobic eukaryotic cells. The circadian clock enhances the fitness of organisms by enabling them to anticipate cycling changes in the surroundings. ROS generation in the cell is often altered in response to environmental changes, but oscillations in ROS levels may also reflect endogenous metabolic fluctuations governed by the circadian clock. On the other hand, an effective regulation and timing of antioxidant mechanisms may be crucial in the defense of cellular integrity. Thus, an interaction between the circadian timekeeping machinery and ROS homeostasis or signaling in both directions may be of advantage at all phylogenetic levels. The Frequency-White Collar-1 and White Collar-2 oscillator (FWO) of the filamentous fungus Neurospora crassa is well characterized at the molecular level. Several members of the ROS homeostasis were found to be controlled by the circadian clock, and ROS levels display circadian rhythm in Neurospora. On the other hand, multiple data indicate that ROS affect the molecular oscillator. Increasing evidence suggests the interplay between ROS homeostasis and oscillators that may be partially or fully independent of the FWO. In addition, ROS may be part of a complex cellular network synchronizing non-transcriptional oscillators with timekeeping machineries based on the classical transcription-translation feedback mechanism. Further investigations are needed to clarify how the different layers of the bidirectional interactions between ROS homeostasis and circadian regulation are interconnected.

Highlights

  • Circadian timekeeping allows organisms to align their physiology with regular upcoming events in their surroundings that vary with a daily cycle

  • Several data indicate an interrelationship between reactive oxygen species (ROS) signaling and the circadian rhythm in Neurospora, that is, ROS levels oscillate in a circadian manner, and vice versa, ROS homeostasis is involved in the control of the circadian rhythm [16, 61, 180, 181]

  • A classical circadian oscillator is based on a translation feedback loops (TTFLs) mechanism, called Frequency-White Collar-1 and White Collar-2 oscillator (FWO) in Neurospora

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Summary

Introduction

Circadian timekeeping allows organisms to align their physiology with regular upcoming events in their surroundings that vary with a daily cycle. The filamentous fungus Neurospora crassa has proven to be extremely useful for dissecting the basic organization of the circadian clock. Besides reflecting physiological fluctuations of the metabolic activity, cellular reactive oxygen species (ROS) levels are highly elevated under oxidative stress situations. Circadian oxidation cycles of peroxiredoxin were shown in multiple organisms including Neurospora [47]. These data suggest that, in addition to the well-described transcription– translation feedback loops (TTFLs), and most probably interacting with them, non-transcriptional oscillations could be common mechanisms of circadian timekeeping. We focus on the oscillations of ROS levels and the data suggesting that the cellular redox state may feedback on the circadian clock

Circadian rhythm in Neurospora
The molecular clock of Neurospora
Light entrainment of the Neurospora clock
Temperature as an input of the circadian clock in Neurospora
Output of the Neurospora clock
Source of ROS in Neurospora
Antioxidant system in Neurospora crassa
ROS homeostasis progressively changes during cell differentiation
Regulation of the antioxidant system in Neurospora crassa
Circadian regulation of the actors of ROS homeostasis
INTERPLAY BETWEEN ROS AND THE NEUROSPORA CIRCADIAN CLOCK
Findings
Conclusions
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