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Crosstalk dynamics between the circadian clock and the mTORC1 pathway
José G Guerrero-Morín1, Moisés Santillán1
1Unidad Monterrey, Centro de Investigación y de Estudios Avanzados del IPN, Apodaca, Nuevo León, Mexico.
Journal of Theoretical Biology
|June 12, 2020
Summary
The mammalian target of rapamycin (mTOR) pathway regulates circadian rhythms. mTORC1 controls circadian clock amplitude via BMAL1 translation and period by regulating BMAL1 localization, ensuring robust oscillations.
Area of Science:
- Biochemistry
- Cellular Biology
- Systems Biology
Background:
- Circadian rhythms and cellular metabolism are interconnected.
- The mammalian target of rapamycin (mTOR) pathway is a key regulator of cell growth and nutrient sensing.
- The circadian clock influences mTOR protein rhythmicity, while mTORC1 affects circadian oscillation properties.
Purpose of the Study:
- To investigate the mechanism by which mTORC1 regulates the core circadian clock.
- To explore interactions between mTORC1 and circadian clock components using mathematical modeling.
Main Methods:
- Development of a deterministic differential-algebraic equation (DAE) model.
- Simulation of circadian clock dynamics under mTORC1 influence.
Main Results:
- mTORC1 regulates circadian clock amplitude by controlling BMAL1 translation.
- mTORC1 tunes circadian clock period by modulating BMAL1 post-translational localization.
- Both translational control and localization regulation of BMAL1 by mTORC1 are necessary for robust circadian oscillations.
Conclusions:
- mTORC1 plays a significant role in modulating circadian rhythms.
- The interplay between mTORC1 and BMAL1 is crucial for maintaining the robustness of cellular oscillations.
- This study provides a mechanistic understanding of mTORC1's influence on circadian clockwork.
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