Roles of Temperature and Reactive Oxygen Species in Circadian Rhythms and Thermosensitivity.

Noxious temperature changes and high levels of reactive oxygen species (ROS) have traditionally been regarded as harmful stimuli. However, there is now substantial evidence for the importance of small-to-moderate changes in temperature and ROS levels-well below the thresholds that induce cell death or physiological dysfunction-as fundamental signaling cues that regulate a wide range of physiological functions in mammals. In this review, I summarize our recent findings on the regulatory roles of slight fluctuations in temperature and intracellular ROS in biological processes. In particular, this review focuses on two key examples: (A) the effects of subtle changes in physiological circadian body temperature fluctuations on the translational efficiency of the core clock gene Period2 and (B) the role of non-toxic levels of ROS as essential intracellular signals that modulate transient receptor potential ion channel activity and cold sensitivity. Our findings challenge longstanding assumptions that circadian clocks are governed solely by transcriptional and post-translational mechanisms and that the temperature sensitivity of ion channels arises exclusively from direct thermal gating. We demonstrated the pivotal roles of the translational control of mRNA and mitochondrial responses in the temperature-mediated maintenance of circadian clock function and ion channel activity. These insights provide conceptual advances relevant to chronobiology, neuroscience, and pharmacology.