Mitochondrial LETM1 Drives Ionic and Molecular Clock Rhythms in Circadian Pacemaker Neurons

Morioka, Eri; Kasuga, Yusuke; Kanda, Yasunari; Moritama, Saki; Koizumi, Hayato; Miura, Nobuhiko; Ikeda, Masaaki; Higashida, Haruhiro; Holmes, Todd C.; Ikeda, Masayuki

doi:10.2139/ssrn.3780282

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“…2), which is consistent with previous work (15), suggesting that circadian Ca 2+ rhythms are regulated by intracellular oscillatory mechanisms and neuronal networks. Recently, Morioka et al (30) reported that the knockdown of a mitochondrial cation antiporter (Leucine zipper-EF-hand-containing transmembrane protein 1: LETM1) in the SCN deteriorated circadian molecular and Ca 2+ rhythms, suggesting that Ca 2+ rhythms in SCN neurons could be associated with mitochondrial ion transport. In contrast, TTX application significantly attenuated the circadian rhythmicity of cAMP (Fig.…”

Section: Discussionmentioning

confidence: 99%

Network-driven intracellular cAMP coordinates circadian rhythm in the suprachiasmatic nucleus

et al. 2023

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The mammalian central circadian clock, located in the suprachiasmatic nucleus (SCN), coordinates the timing of physiology and behavior to local time cues. In the SCN, second messengers, such as cAMP and Ca 2+ , are suggested to be involved in the input and/or output of the molecular circadian clock. However, the functional roles of second messengers and their dynamics in the SCN remain largely unclear. In the present study, we visualized the spatiotemporal patterns of circadian rhythms of second messengers and neurotransmitter release in the SCN. Here, we show that neuronal activity regulates the rhythmic release of vasoactive intestinal peptides from the SCN, which drives the circadian rhythms of intracellular cAMP in the SCN. Furthermore, optical manipulation of intracellular cAMP levels in the SCN shifts molecular and behavioral circadian rhythms. Together, our study demonstrates that intracellular cAMP is a key molecule in the organization of the SCN circadian neuronal network.

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Section: Discussionmentioning

confidence: 99%