Abstract
Macroautophagy is a vacuolar, self-digesting mechanism responsible for the removal of long-lived proteins and damaged organelles by the lysosome. The discovery of the ATG genes has provided key information about the formation of the autophagosome, and about the role of macroautophagy in allowing cells to survive during nutrient depletion and/or in the absence of growth factors. Two connected signaling pathways encompassing class-I phosphatidylinositol 3-kinase and (mammalian) target of rapamycin play a central role in controlling macroautophagy in response to starvation. However, a considerable body of literature reports that macroautophagy is also a cell death mechanism that can occur either in the absence of detectable signs of apoptosis (via autophagic cell death) or concomitantly with apoptosis. Macroautophagy is activated by signaling pathways that also control apoptosis. The aim of this review is to discuss the signaling pathways that control macroautophagy during cell survival and cell death.
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Abbreviations
- AICAR:
-
5-aminoimidazole-4-carboxamide riboside
- AMPK:
-
AMP-activated protein kinase
- DAP kinase:
-
death-associated protein kinase
- DAPK:
-
death-associated protein kinase
- DRP-1:
-
death-associated related protein kinase-1
- eIF2α:
-
eukaryotic initiation factor-2 alpha
- 4E-BP1:
-
eukaryotic translational initiation factor 4E-binding protein-1
- ERK:
-
extracellular signal-regulated protein kinase
- FADD:
-
Fas-associated death domain protein
- GAIP:
-
G alpha interacting protein
- GFP:
-
green fluorescent protein
- LC3:
-
light chain 3
- 3-MA:
-
3-methyladenine
- MAPK:
-
mitogen-activated protein kinase
- mTOR:
-
(mammalian) target of rapamycin
- PDK1:
-
phosphoinositide-dependent kinase-1
- PI3K:
-
phosphatidylinositol 3-kinase
- PI(3)P:
-
phosphatidylinositol 3-phosphate
- PI(3,4)P2:
-
phosphatidylinositol 3,4, bisphosphate
- PI(3,4,5)P3:
-
phosphatidylinositol-3,4,5-trisphosphate
- PKB:
-
protein kinase B
- PKR:
-
double-stranded RNA-activated protein kinase
- PTEN:
-
phosphatase and tensin homolog deleted from chromosome 10
- Rheb:
-
Ras homolog enriched in brain
- RIP:
-
receptor-interacting-protein
- ROS:
-
reactive oxygen species
- S6:
-
ribosomal protein S6
- S6K or p70S6K:
-
70 kDa S6 kinase
- TNF:
-
tumor necrosis factor
- TRAIL:
-
TNF-related apoptosis-inducing factor
- TSC:
-
tuberous sclerosis complex
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Acknowledgements
We would like to apologize to any authors whose work could not be cited here because of space limitation. Work in P Codogno's laboratory is supported by institutional funding from The Institut National de la Santé et de la Recherche Médicale (INSERM) and grants from the Association pour la Recherche sur le Cancer (ARC 3503).
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Codogno, P., Meijer, A. Autophagy and signaling: their role in cell survival and cell death. Cell Death Differ 12 (Suppl 2), 1509–1518 (2005). https://doi.org/10.1038/sj.cdd.4401751
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DOI: https://doi.org/10.1038/sj.cdd.4401751
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