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Forkhead Box O (FoxO) Transcription Factors in Autophagy, Metabolic Health, and Tissue Homeostasis

  • Longhua Liu
  • Zhiyong Cheng
Chapter
Part of the Stem Cell Biology and Regenerative Medicine book series (STEMCELL)

Abstract

As transcription factors, the forkhead box O family proteins control the expression of genes that are involved in the regulation of autophagy and metabolism. The FoxO–autophagy axis has been shown to mediate cell differentiation and tissue development. Dysregulated FoxO activity may compromise tissue development and homeostasis, concomitant with metabolic abnormalities across tissues such as liver, adipose tissue, skeletal muscle, and heart. In this chapter, we discuss the mechanism or pathways of FoxO transcription factors regulating autophagy and tissue integrity, and the FoxO–autophagy axis in cellular metabolism and fate determination. The evidence summarized here suggests that targeting the FoxO–autophagy axis may lead to therapeutic options for metabolic derangements and cell or tissue dysfunction.

Keywords

Autophagy FoxO Cell differentiation Development Metabolism Tissue homeostasis 

Abbreviations

ACO

Acyl-CoA oxidase

Akt (or PKB)

Protein kinase B

AMPK

AMP-activated protein kinase

Atg

Autophagy related protein

C/EBP

CCAAT/enhancer-binding protein

CD36

Fatty acid translocase FAT/cluster of differentiation 36

CMV

Controlled mechanical ventilation

CREB

cAMP response element binding protein

DBD

DNA binding domain

ER

Endoplasmic reticulum

FoxO

Forkhead box O

FSP27

Fat-specific protein 27

G6Pase

Glucose-6-phosphatase

HDAC

Histone deacetylase

HK

Hexokinase

JNK

c-Jun N-terminal kinase

KAA

Ketogenic amino acid

LC3

Microtubule-associated protein 1A/1B-light chain 3-phosphatidylethanolamine conjugate

LDHA

Lactate dehydrogenase A

LXR

Liver X receptor

MI

Myocardial infarction

MST1

Mammalian sterile 20-like kinase 1

mTORC1

Mammalian target of rapamycin complex 1

MTP

Microsomal tryglyceride transfer protein

MuRF1

Muscle RING-finger protein-1

NES

Nuclear export sequence

NLS

Nuclear localization signal

Pdx1

Pancreas/duodenum homeobox gene-1

PEPCK

Phosphoenolpyruvate carboxykinase

PGC1

Peroxisome proliferator-activated receptor gamma coactivator 1

PI3K

Phosphatidylinositol 3 kinase

PI3P

Phoshpatidylinositol 3-phosphate

PKA

Protein kinase A

PKM2

Pyruvate kinase isozymes M2

PPARγ

Peroxisome proliferator-activated receptor γ

RXR

Retinoid X receptor

Sirt1,2

sirtuin 1, 2

SKP2

S-phase kinase-associated protein 2

SQSTM1 (or p62)

Sequestosome 1

SREBP

Sterol response element-binding protein

STZ

Streptozotocin

Tfeb

Transcription factor EB

ULK

Unc-51-like kinase

VLDL

Very-low-density lipoprotein

Vps34

Vacuolar proteins 34

Notes

Acknowledgments

This work was supported by USDA National Institute of Food and Agriculture Hatch Project 1007334 (ZC) and American Heart Association Grant 18TPA34230082 (ZC) . The authors declare no potential conflict of interest.

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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Department of Human Nutrition, Foods, and Exercise, Fralin Life Science Institute, College of Agriculture and Life ScienceVirginia TechBlacksburgUSA
  2. 2.Department of Pathology & Cell Biology, Columbia Diabetes Research Center, New York Obesity Research CenterColumbia UniversityNew YorkUSA

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