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Activating Autophagy by Aerobic Exercise in Mice
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Keeping the autophagy tempo.

Nunzia Pastore1,2, Andrea Ballabio1,2,3,4

  • 1Jan and Dan Duncan Neurological Research Institute, Texas Children Hospital , Houston , TX , USA.

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|July 19, 2019
PubMed
Summary
This summary is machine-generated.

Mammalian physiological functions, including autophagy, exhibit daily rhythms. Transcription factors TFEB and TFE3 link nutrient intake to the molecular clock by regulating NR1D1/REV-ERBα, controlling autophagy and metabolism oscillations.

Keywords:
AutophagyNR1D1/REV-ERBαTFEB/TFE3circadian rhythmgene oscillation

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Area of Science:

  • Cellular Biology
  • Chronobiology
  • Molecular Biology

Background:

  • Mammalian physiological functions, such as sleep-wake cycles and metabolism, exhibit robust 24-hour circadian rhythms.
  • Recent research demonstrates that macroautophagy/autophagy also follows a circadian pattern, closely linked to daily feeding schedules in adult mammals.

Purpose of the Study:

  • To elucidate the molecular mechanisms connecting nutrient-driven circadian rhythms with the light-entrained molecular clock.
  • To identify the key regulators responsible for the circadian control of autophagy and metabolic gene expression.

Main Methods:

  • Investigated the role of MiT-TFE transcription factors (TFEB and TFE3) in circadian regulation.
  • Analyzed the activation patterns of TFEB and TFE3 in relation to autophagy and lysosomal biogenesis.
  • Examined the regulatory relationship between TFEB/TFE3 and NR1D1/REV-ERBα, a core clock component.

Main Results:

  • TFEB and TFE3, master regulators of autophagy, are activated in a circadian manner.
  • These transcription factors were found to drive the expression of NR1D1/REV-ERBα, a key element of the core circadian clock.
  • A molecular link was established between nutrient-driven circadian cycles and the light-induced molecular clock.

Conclusions:

  • The dynamic interplay between TFEB/TFE3 activation and NR1D1 expression orchestrates the rhythmic modulation of autophagy and metabolism genes.
  • This study reveals a novel regulatory axis integrating nutrient sensing with the central circadian clockwork to control fundamental physiological processes.