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

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Autophagy in Health and Disease

Part of the book series: Stem Cell Biology and Regenerative Medicine ((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.

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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

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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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  1. Longhua Liu

    Present address: Department of Pathology & Cell Biology, Columbia Diabetes Research Center, New York Obesity Research Center, Columbia University, New York, NY, USA

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  1. Department of Human Nutrition, Foods, and Exercise, Fralin Life Science Institute, College of Agriculture and Life Science, Virginia Tech, Blacksburg, VA, USA

    Longhua Liu & Zhiyong Cheng

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  2. Zhiyong Cheng
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Correspondence to Zhiyong Cheng .

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    Kursad Turksen

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Liu, L., Cheng, Z. (2018). Forkhead Box O (FoxO) Transcription Factors in Autophagy, Metabolic Health, and Tissue Homeostasis. In: Turksen, K. (eds) Autophagy in Health and Disease. Stem Cell Biology and Regenerative Medicine. Humana Press, Cham. https://doi.org/10.1007/978-3-319-98146-8_4

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