Mitochondrial LETM1 drives ionic and molecular clock rhythms in circadian pacemaker neurons

The mechanisms that generate robust ionic oscillation in circadian pacemaker neurons are under investigation. Here, we demonstrate critical functions of the mitochondrial cation antiporter leucine zipper-EF-hand-containing transmembrane protein 1 (LETM1), which exchanges K /H in Drosophila and Ca /H...

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Published in:Cell reports (Cambridge) 2022-05, Vol.39 (6), p.110787-110787, Article 110787
Main Authors: Morioka, Eri, Kasuga, Yusuke, Kanda, Yuzuki, Moritama, Saki, Koizumi, Hayato, Yoshikawa, Tomoko, Miura, Nobuhiko, Ikeda, Masaaki, Higashida, Haruhiro, Holmes, Todd C, Ikeda, Masayuki
Format: Article
Language:English
Subjects:
Animals
Circadian Rhythm - physiology
Drosophila - physiology
Mammals
Mitochondria - metabolism
Neurons - metabolism
Rats
Suprachiasmatic Nucleus - metabolism
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Summary:The mechanisms that generate robust ionic oscillation in circadian pacemaker neurons are under investigation. Here, we demonstrate critical functions of the mitochondrial cation antiporter leucine zipper-EF-hand-containing transmembrane protein 1 (LETM1), which exchanges K /H in Drosophila and Ca /H in mammals, in circadian pacemaker neurons. Letm1 knockdown in Drosophila pacemaker neurons reduced circadian cytosolic H rhythms and prolonged nuclear PERIOD/TIMELESS expression rhythms and locomotor activity rhythms. In rat pacemaker neurons in the hypothalamic suprachiasmatic nucleus (SCN), circadian rhythms in cytosolic Ca and Bmal1 transcription were dampened by Letm1 knockdown. Mitochondrial Ca uptake peaks late during the day were also observed in rat SCN neurons following photolytic elevation of cytosolic Ca . Since cation transport by LETM1 is coupled to mitochondrial energy synthesis, we propose that LETM1 integrates metabolic, ionic, and molecular clock rhythms in the central clock system in both invertebrates and vertebrates.
ISSN:2211-1247
2211-1247
DOI:10.1016/j.celrep.2022.110787