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Macroautophagy Signaling and Regulation

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Autophagy in Infection and Immunity

Part of the book series: Current Topics in Microbiology and Immunology ((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.

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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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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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© 2009 Springer-Verlag Berlin Heidelberg

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Esclatine, A., Chaumorcel, M., Codogno, P. (2009). Macroautophagy Signaling and Regulation. In: Levine, B., Yoshimori, T., Deretic, V. (eds) Autophagy in Infection and Immunity. Current Topics in Microbiology and Immunology, vol 335. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-00302-8_2

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