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AMPK and Autophagy

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Autophagy: Biology and Diseases

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1206))

Abstract

AMPK is an evolutionarily conserved serine/threonine-protein kinase that acts as an energy sensor in cells and plays a key role in the upregulation of catabolism and inactivation of anabolism. Under various physiological and pathological conditions, AMPK can be phosphorylated by an upstream kinase and bind to AMP or ADP rather than ATP, leading to its activation. Activated AMPK regulates a variety of metabolic processes, including autophagy. AMPK promotes autophagy directly by phosphorylating autophagy-related proteins in the mTORC1, ULK1, and PIK3C3/VPS34 complexes or indirectly by regulating the expression of autophagy-related genes downstream of transcription factors such as FOXO3, TFEB, and BRD4. AMPK can also upregulate the autophagic degradation of mitochondria (mitophagy), as it can induce fragmentation of damaged mitochondria in the network and promote the translocation of the autophagy machinery to damaged mitochondria. In this section, we will detail the molecular structure of AMPK, how its activity is regulated, and its pivotal role in regulating autophagy and mitophagy.

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Abbreviations

ACC:

Acetyl-CoA carboxylase

ACSS2:

Acetyl-CoA synthetase 2

ADaM:

Allosteric drug and metabolite

ADP:

Adenosine diphosphate

AICAR:

5-aminoimidazole-4-carboxamide riboside

AMP:

Adenosine monophosphate

AMPK:

AMP-activated protein kinase

ATP:

Adenosine triphosphate

ATG:

Autophagy-related gene

BMDM:

Bone marrow-derived macrophages

BRD4:

Bromodomain-containing protein 4

CAMKK2:

Calmodulin-dependent protein kinases kinase 2

CARM1:

Coactivator-associated arginine (R) methyltransferase 1

CBD:

Carbohydrate-binding domain

CBS:

Cystathionine β-synthase

CHOP:

C/EBP homologous protein

CCCP:

Carbonyl cyanide 3-chlorophenylhydrazone

DDIT3:

DNA damage-inducible transcript 3

DRP1:

Dynamin-related protein 1

FAS:

Fatty acid synthase

FOXK:

Forkhead box protein K

FOXO3:

Forkhead box O3

FUNDC1:

FUN14 domain-containing protein 1

GAP:

GTPase-activating protein

GBD:

Glycogen-binding domain

GDP:

Guanine dinucleotide phosphate

GLUT4:

Glucose Transporter 4

GPAT:

Glycerol phosphate acyltransferase

GSK3β:

Glycogen synthase kinase 3 beta

GTP:

Guanine trinucleotide phosphate

HSF1:

Heat shock factor 1

IGF-1:

Insulin-like growth factor 1

LKB1:

Liver kinase B1

MAPKK:

Mitogen-activated protein kinase kinase

MEF:

Mouse embryonic fibroblasts

MFF:

Mitochondrial fission factor

MO25:

Mouse protein 25

mtDNA:

Mitochondrial DNA

mTOR:

Mammalian target of rapamycin

NBS:

Nucleotide-binding site

NES:

Nuclear export sequence

NMT1:

N-myristoyl transferase 1

NRF2:

Nuclear factor erythroid 2-related factor 2

PAQR3:

Progestin and adipo-Q receptor 3

PGC1α:

PPARγ coactivator 1α

PI3P:

Phosphatidylinositol 3-phosphate

PIK3C3:

Phosphatidylinositol 3-kinase catalytic subunit 3

PIK3R4:

Phosphoinositide 3-kinase regulatory subunit 4

PINKl:

PTEN induced kinase 1

PKA:

Protein kinase A

PKB:

Protein kinase B

PKC:

Protein kinase C

PKD:

Protein kinase D

PP2A:

Protein phosphatase 2A

PPARγ:

Peroxisome proliferator-activated receptor γ

PPM1E:

Protein Phosphatase, Mg2+/Mn2+-Dependent 1E

PRKAA:

AMP-activated protein kinase catalytic subunit alpha

PRKAB:

AMP-activated protein kinase subunit beta

PRKAG:

AMP-activated protein kinase subunit gamma

RACK1:

Receptor for activated C kinase 1

RB1CC1:

RB1-inducible coiled-coil 1

RHEB:

Ras Homolog Enriched in Brain

RNS:

Reactive nitrogen species

ROS:

Reactive oxygen species

SKP2:

S-phase kinase-associated protein 2

STK11:

Serine/Threonine kinase 11

STRAD:

Ste20-related adaptor protein

TAK1:

Transforming growth factor-β-activating kinase 1

TCA:

Tricarboxylic acid cycle

TFEB:

Transcription Factor EB

TNFSF10:

TNF superfamily member 10

TRAIL:

TNF-related apoptosis inducing ligand

TSC:

Tuberous sclerosis complex

TZD:

Thiazolidinediones,

ULK1:

Unc-51-like kinase 1

UVRAG:

Ultraviolet radiation resistance‑associated gene protein

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Authors and Affiliations

  1. College of Life Sciences, Nankai University, Tianjin, China

    Yanjun Li

  2. Department of Immunology, Peking University School of Basic Medical Sciences, NHC Key Laboratory of Medical Immunology, Peking University, Beijing, China

    Yingyu Chen

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  1. Yanjun Li
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  2. Yingyu Chen
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Correspondence to Yingyu Chen .

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Editors and Affiliations

  1. Jiangsu Key Laboratory of Neuropsychiatric Diseases, Department of Pharmacology and Laboratory of Aging and Nervous Diseases, College of Pharmaceutical Sciences of Soochow University, Suzhou, China

    Zheng-Hong Qin

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Li, Y., Chen, Y. (2019). AMPK and Autophagy. In: Qin, ZH. (eds) Autophagy: Biology and Diseases. Advances in Experimental Medicine and Biology, vol 1206. Springer, Singapore. https://doi.org/10.1007/978-981-15-0602-4_4

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