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Mitochondrial LETM1 drives ionic and molecular clock rhythms in circadian pacemaker neurons
Eri Morioka1, Yusuke Kasuga1, Yuzuki Kanda1
1Graduate School of Science and Engineering, University of Toyama, Gofuku, Toyama 930-8555, Japan.
Cell Reports
|May 11, 2022
Summary
The mitochondrial protein LETM1 (leucine zipper-EF-hand-containing transmembrane protein 1) is crucial for maintaining robust ionic rhythms in circadian pacemaker neurons. Its function is vital for regulating the internal body clock in both flies and mammals.
Area of Science:
- Chronobiology
- Mitochondrial Biology
- Neuroscience
Background:
- Circadian rhythms are fundamental biological processes regulated by pacemaker neurons.
- Ionic oscillations within these neurons are critical for robust rhythm generation.
- The precise mechanisms underlying these ionic rhythms remain incompletely understood.
Purpose of the Study:
- To investigate the role of the mitochondrial cation antiporter LETM1 (leucine zipper-EF-hand-containing transmembrane protein 1) in circadian pacemaker neurons.
- To determine LETM1's function in regulating ionic rhythms and molecular clock components.
- To explore LETM1's contribution to the integration of metabolic and circadian processes.
Main Methods:
- Utilized knockdown of Letm1 in Drosophila pacemaker neurons.
- Examined circadian rhythms of cytosolic H+, nuclear PERIOD/TIMELESS expression, and locomotor activity.
- Investigated Letm1 knockdown effects on cytosolic Ca2+ and Bmal1 transcription in rat suprachiasmatic nucleus (SCN) neurons.
- Observed mitochondrial Ca2+ uptake dynamics in rat SCN neurons.
Main Results:
- Letm1 knockdown in Drosophila disrupted cytosolic H+ rhythms and prolonged molecular clock and activity rhythms.
- In rat SCN neurons, Letm1 knockdown dampened circadian rhythms of cytosolic Ca2+ and Bmal1 transcription.
- Mitochondrial Ca2+ uptake showed distinct late-day peaks in rat SCN neurons.
- LETM1's cation transport function is linked to mitochondrial energy synthesis.
Conclusions:
- LETM1 plays a critical role in maintaining ionic oscillations within circadian pacemaker neurons.
- LETM1 is essential for regulating molecular clock components and behavioral rhythms.
- LETM1 integrates metabolic, ionic, and molecular rhythms, acting as a key component of the central clock system in both invertebrates and vertebrates.
Keywords:
CP: MetabolismCP: Neurosciencecaged Ca(2+) compoundcircadian H(+) rhythmsclock geneslateral neuronsmitochondrial calcium imagingproton imagingMore Related Videos
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