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Macroautophagy Signaling and Regulation

Chapter
First Online:
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 335)

Abstract

Macroautophagy is a vacuolar degradation pathway that terminates in the lysosomal compartment. Macroautophagy is a multistep process involving: (1) signaling events that occur upstream of the molecular machinery of autophagy; (2) molecular machinery involved in the formation of the autophagosome, the initial multimembrane-bound compartment formed in the autophagic pathway; and (3) maturation of autophagosomes, which acquire acidic and degradative capacities. In this chapter we summarize what is known about the regulation of the different steps involved in autophagy, and we also discuss how macroautophagy can be manipulated using drugs or genetic approaches that affect macroautophagy signaling, and the subsequent formation and maturation of the autophagosomes. Modulating autophagy offers a promising new therapeutic approach to human diseases that involve macroautophagy.

Keywords

Endoplasmic Reticulum Stress Phosphatidyl Ethanolamine Autophagic Cell Death Autophagosome Formation Lysosomal Compartment 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

3-MA

3-Methyladenine

4E-BP1

Eukaryotic translational initiation factor 4E-binding protein 1

AMPK

AMP-activated protein kinase

ATG

Autophagy-related

DAP kinase

Death-associated protein kinase

DRAM

Damage-regulated autophagy modulator

DRP-1

Death-associated related protein kinase 1

eIF2α

Eukaryotic initiation factor 2 alpha

ERK

Extracellular signal-regulated protein kinase

FDA

Food and drug administration

JNK

c-Jun N-terminal kinase

LC3

Light chain 3

MAPK

Mitogen-activated protein kinase

(m)TOR

(Mammalian) target of rapamycin

PE

Phosphatidyl ethanolamine

PERK

Protein kinase R-like endoplasmic reticulum kinase

PI3K

Phosphatidylinositol 3-phosphate kinase

PKR

Double-stranded RNA-activated protein kinase

Rheb

Ras homolog enriched in brain

ROS

Reactive oxygen species

SNARE

Soluble NSF attachment protein receptors

TSC

Tuberous sclerosis complex

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Notes

Acknowledgments

Work in P. Codogno’s laboratory is supported by institutional funding from The Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Sud 11, and grants from the Agence Nationale de la Recherche (ANR to A.E.) and the Association pour la Recherche sur le Cancer (ARC to P.C.). M.C. is the recipient of a Ph.D. fellowship from the French Ministry of Research.

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Authors and Affiliations

  1. 1.INSERM U756Université Paris-Sud 11, Faculté de PharmacieChâtenay-MalabryFrance

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