The Autophagy-related Gene 14 (Atg14) Is Regulated by Forkhead Box O Transcription Factors and Circadian Rhythms and Plays a Critical Role in Hepatic Autophagy and Lipid Metabolism*

  title={The Autophagy-related Gene 14 (Atg14) Is Regulated by Forkhead Box O Transcription Factors and Circadian Rhythms and Plays a Critical Role in Hepatic Autophagy and Lipid Metabolism*},
  author={Xiwen Xiong and Rongya Tao and Ronald A. DePinho and X. Charlie Dong},
  journal={The Journal of Biological Chemistry},
  pages={39107 - 39114}
Background: Atg14 is critical for the autophagy initiation. Results: Our data show that the Atg14 gene can be regulated by FoxO and Clock transcription factors, and it has striking impacts on hepatic autophagy and triglycerides. Conclusion: Atg14 is controlled by FoxOs and circadian rhythms, and it modulates hepatic lipid homeostasis. Significance: These findings suggest that Atg14 is crucial for hepatic autophagy and lipid metabolism. Autophagy plays a critical role in cell survival from… 

Identification of transcription factors that regulate ATG8 expression and autophagy in Arabidopsis

A yeast one-hybrid screen for transcription factors (TFs) that regulate ATG8 gene expression in Arabidopsis, using the promoters of 4 ATG 8 genes provides a comprehensive resource of TFs and lays a foundation for understanding the transcriptional regulation of plant autophagy.

From the Cover: Autophagy Induction Contributes to Cadmium Toxicity in Mesenchymal Stem Cells via AMPK/FOXO3a/BECN1 Signaling.

  • Min YangH. Pi Zhou Zhou
  • Biology, Chemistry
    Toxicological sciences : an official journal of the Society of Toxicology
  • 2016
Results demonstrate that Cd-induced cell death via the overactivation of FOXO3a-dependent autophagy pathway may offer novel therapeutic approaches for the treatment of C d-induced bone damage.

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This paper highlights the main cellular regulators of transcription factors that are involved in mammalian autophagy and their target genes and investigates their interplay and timing.

GA binding protein augments autophagy via transcriptional activation of BECN1-PIK3C3 complex genes

Macroautophagy is a vesicular catabolic trafficking pathway that is thought to protect cells from diverse stressors and to promote longevity. Recent studies have revealed that transcription factors

The interplay of microRNAs and transcription factors in autophagy regulation in nonalcoholic fatty liver disease

The interplay of miRNAs and TFs in regulating the activity of genes involved in autophagy and specifically its impairment in nonalcoholic fatty liver disease (NAFLD) is reviewed.

Detection of WIPI1 mRNA as an indicator of autophagosome formation

The identification of several ATG genes, including the genes ULK1, MAP1LC3B, GABARAPL1, ATG13, WIPI1, and WDR45/WIPI4, with elevated mRNA levels in thapsigargin-, C2-ceramide-, and rapamycin-treated as well as amino acid-depleted HeLa cells are identified.

Nr1d1 affects autophagy in the skeletal muscles of juvenile Nile tilapia by regulating the rhythmic expression of autophagy-related genes

Evidence is provided that nutritional deficiency affects both circadian regulation and autophagy activities in skeletal muscle in fasted fish.

Critical role of FoxO3a in alcohol-induced autophagy and hepatotoxicity.


Temporal orchestration of circadian autophagy rhythm by C/EBPβ

C/EBPβ is identified as a key factor that links autophagy to biological clock and maintains nutrient homeostasis throughout light/dark cycles and is disrupted in mice lacking a functional liver clock.

The unfolded protein response protects human tumor cells during hypoxia through regulation of the autophagy genes MAP1LC3B and ATG5.

It is demonstrated that the UPR is an important mediator of the hypoxic tumor microenvironment and that it contributes to resistance to treatment through its ability to facilitate autophagy.

Cytosolic FoxO1 is essential for the induction of autophagy and tumour suppressor activity

It is reported that cytosolic FoxO1, a forkhead O family protein, is a mediator of autophagy and associated with tumour suppressor activity in human colon tumours and a xenograft mouse model.

Deacetylation of FoxO by Sirt1 Plays an Essential Role in Mediating Starvation-Induced Autophagy in Cardiac Myocytes

It is suggested that Sirt1-mediated deacetylation of FoxO1 and upregulation of Rab7 play an important role in mediating starvation-induced increases in autophagic flux, which in turn plays an essential role in maintaining left ventricular function during starvation.

FoxO Transcription Factors Promote Autophagy in Cardiomyocytes*

Evidence is provided for an important role for FoxO1 and FoxO3 in regulating autophagy and cell size in cardiomyocytes and in vivo studies show that cellular stress, such as starvation or ischemia/reperfusion in mice, results in induction ofAutophagy in the heart with concomitant dephosphorylation of FoxO, consistent with increased activity of nuclear FoxO transcription factors.

Distinct regulation of autophagic activity by Atg14L and Rubicon associated with Beclin 1–phosphatidylinositol-3-kinase complex

It is hypothesized that by forming distinct protein complexes, Beclin 1 and its binding proteins orchestrate the precise function of the class III PI(3)K in regulating autophagy at multiple steps.

Modulation of glutamine metabolism by the PI(3)K–PKB–FOXO network regulates autophagy

A growth-factor-responsive network that can directly modulate autophagy through the regulation of glutamine metabolism is revealed, suggesting that the induction ofautophagy by FOXO3-mediated glutamine synthetase expression is important for cellular survival.

E2F1 regulates autophagy and the transcription of autophagy genes

It is shown here that activation of E2F1 upregulates the expression of four autophagy genes—microtubule-associated protein-1 light chain-3 (LC3), Autophagy-related gene-1 (ATG1), ATG1, ATG5 and damage-regulated autophagic modulator (DRAM) and for the first time, a role for E2f1 in DNA damage-inducedAutophagy is established.

Identification of Barkor as a mammalian autophagy-specific factor for Beclin 1 and class III phosphatidylinositol 3-kinase

A regulatory signaling pathway mediated by Barkor that positively controls autophagy through Beclin 1 is defined and represents a potential target for drug development in the treatment of human diseases implicated in autophagic dysfunction.