Abstract
Apoptosis and autophagy are two evolutionary conserved processes that exert a critical role in the maintenance of tissue homeostasis. While apoptosis is a tightly regulated cell program implicated in the removal of damaged or unwanted cells, autophagy is a cellular catabolic pathway that is involved in the lysosomal degradation and recycling of proteins and organelles, and is thereby considered an important cytoprotection mechanism. Sphingolipids (SLs), which are ubiquitous membrane lipids in eukaryotes, participate in the generation of various membrane structures, including lipid rafts and caveolae, and contribute to a number of cellular functions such as cell proliferation, apoptosis and, as suggested more recently, autophagy. For instance, SLs are hypothesized to be involved in several intracellular processes, including organelle membrane scrambling, whilst at the plasma membrane lipid rafts, acting as catalytic domains, strongly contribute to the ignition of critical signaling pathways determining cell fate. In particular, by targeting several shared regulators, ceramide, sphingosine-1-phosphate, dihydroceramide, sphingomyelin and gangliosides seem able to differentially regulate the autophagic pathway and/or contribute to the autophagosome formation. This review illustrates recent studies on this matter, particularly lipid rafts, briefly underscoring the possible implication of SLs and their alterations in the autophagy disturbances and in the pathogenesis of some human diseases.
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Abbreviations
- AMP:
-
Adenosine monophosphate
- AMPK:
-
AMP kinase
- ATG:
-
Autophagy-related gene
- ATP:
-
Adenosine triphosphate
- Bax:
-
BCL2-associated X protein
- Bcl-2:
-
B cell lymphoma 2
- BH3:
-
Bcl-2 homology domain 3
- Bnip3:
-
Bcl-2/adenovirus E1B nineteen kilodalton interacting protein 3
- CDases:
-
Ceramidases
- Cer:
-
Ceramide
- CerS:
-
Ceramide synthase
- CERT:
-
Cer, transfer protein
- CMA:
-
Chaperone-mediated autophagy
- DES:
-
Dihydroceramide desaturase
- dhCer:
-
Dihydroceramide
- dhCerS:
-
Dihydroceramide synthase
- DR:
-
Death receptor
- DRAM:
-
Damage-regulated autophagy modulator
- EGFR:
-
Epidermal growth factor receptor
- ER:
-
Endoplasmic reticulum
- ERK:
-
Extracellular signal-regulated kinase
- FAPP2:
-
Four-phosphate adaptor protein 2
- FLIP:
-
FLICE inhibitor protein
- GCase:
-
Glucocerebrosidase
- GCS:
-
Glucosylceramide synthase
- GD:
-
Gaucher disease
- IKBKB:
-
IκB kinase β
- IKK:
-
Inhibitor of kappa B kinase
- IL-1:
-
Interleukin-1
- JNK:
-
Jun N-terminal kinase
- LAMP1:
-
Lysosomal-associated membrane protein 1
- LC3:
-
Microtubule-associated protein light chain 3
- LDL:
-
Low density lipoprotein
- MAMs:
-
Mitochondria-associated membranes
- MAPK:
-
Mitogen activated protein kinase
- MMP:
-
Mitochondrial membrane permeability
- Mtor:
-
Mechanistic target of rapamycin
- NF-kB:
-
Nuclear factor kappa B
- NPC:
-
Niemann–Pick disease type C
- PE:
-
Phosphatidyl-ethanolamine
- PI3K/AKT:
-
Phosphatidylinositol-3-kinases/AKT
- PtdIns(3)P:
-
Phosphatidylinositol 3-phospate
- ROS:
-
Reactive oxygen species
- S1P:
-
Sphingosine-1-phosphate
- S1P lyase:
-
Sphingosine-1-phosphate lyase
- Sap C:
-
Saposin C
- SLs:
-
Sphingolipids
- SM:
-
Sphingomyelin
- SMases:
-
Sphingomyelinases
- SMS:
-
Sphingomyelin synthase
- SphKs:
-
Sphingosine kinases
- SPPs:
-
Sphingosine-1-phosphate phosphatases
- THC:
-
Cannabinoid tetrahydrocannabinol
- TNF-α:
-
Tumor necrosis factor-α
- TRAIL:
-
Tumor necrosis factor-alpha-related apoptosis-inducing ligand
- ULK1:
-
Unc-51-like kinase 1
- UV:
-
Ultraviolet
- UVRAG:
-
Activating molecule in Beclin-1 regulated autophagy
- VEGFR:
-
Vascular endothelial growth factor receptor
- Vps:
-
Vacuolar protein sorting
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Partially supported by Peretti Foundation, Arcobaleno Onlus and AIRC.
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Chiara Tommasino and Matteo Marconi to be considered as first authors.
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Tommasino, C., Marconi, M., Ciarlo, L. et al. Autophagic flux and autophagosome morphogenesis require the participation of sphingolipids. Apoptosis 20, 645–657 (2015). https://doi.org/10.1007/s10495-015-1102-8
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DOI: https://doi.org/10.1007/s10495-015-1102-8