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Study of Protein-protein Interactions in Autophagy Research
Published on: September 9, 2017
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Nutrient-sensing nuclear receptors coordinate autophagy
Jae Man Lee1, Martin Wagner1, Rui Xiao1
1Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Nature
|November 11, 2014
Summary
Nutrient receptors PPARα and FXR control liver autophagy. PPARα promotes autophagy in fed states, while FXR suppresses it in fasted states, revealing key transcriptional regulation mechanisms.
Area of Science:
- Cellular Biology
- Metabolism
- Molecular Endocrinology
Background:
- Autophagy is a conserved process for nutrient recycling and energy homeostasis.
- While acute regulation of autophagy is understood, its long-term transcriptional control remains unclear.
- Nuclear receptors PPARα (fasted liver) and FXR (fed liver) are key nutrient sensors.
Purpose of the Study:
- To investigate the roles of PPARα and FXR in the transcriptional regulation of hepatic autophagy in mice.
- To elucidate how these nuclear receptors modulate autophagy in response to nutrient status (fasting vs. feeding).
Main Methods:
- Utilized pharmacological activation of PPARα and FXR in wild-type mice.
- Employed knockout mouse models (Ppara(-/-) and Fxr(-/-)) to assess functional roles.
- Analyzed transcriptional regulation by examining promoter binding and gene expression related to autophagy.
Main Results:
- PPARα activation reversed fed-state autophagy suppression, inducing lipophagy, a response absent in Ppara(-/-) mice.
- FXR activation suppressed fasting-state autophagy induction, a response absent in Fxr(-/-) mice.
- PPARα and FXR were found to compete for binding to shared autophagic gene promoters, exerting opposing transcriptional effects.
Conclusions:
- PPARα and FXR are critical regulators of hepatic autophagy, responding to nutrient availability.
- These receptors provide complementary, interlocking transcriptional mechanisms for controlling autophagy based on nutritional status.
- Findings reveal novel insights into the long-term regulation of autophagy beyond acute signaling pathways.
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