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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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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