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Receptor‐Interacting Protein Kinase 3 (RIPK3) inhibits autophagic flux during necroptosis in intestinal epithelial cells
- Source :
- FEBS Letters. 594:1586-1595
- Publication Year :
- 2020
- Publisher :
- Wiley, 2020.
-
Abstract
- Autophagy is an intracellular process that regulates the degradation of cytosolic proteins and organelles. Dying cells often accumulate autophagosomes. However, the mechanisms by which necroptotic stimulation induces autophagosomes are not defined. Here, we demonstrate that the activation of necroptosis with TNF-α plus the cell-permeable pan-caspase inhibitor Z-VAD induces LC3-II and LC3 puncta, markers of autophagosomes, via the receptor-interacting protein kinase 3 (RIPK3) in intestinal epithelial cells. Surprisingly, necroptotic stimulation reduces autophagic activity, as evidenced by enlarged puncta of the autophagic substrate SQSTM1/p62 and its increased colocalization with LC3. However, necroptotic stimulation does not induce the lysosomal-associated membrane protein 1 (LAMP1) nor syntaxin 17, which mediates autophagosome-lysosome fusion, to colocalize with LC3. These data indicate that necroptosis attenuates autophagic flux before the lysosome fusion step. Our findings may provide insights into human diseases involving necroptosis.
- Subjects :
- Necroptosis
Biophysics
Syntaxin 17
Biochemistry
03 medical and health sciences
Structural Biology
Cell Line, Tumor
Lysosome
Sequestosome-1 Protein
Autophagy
Genetics
medicine
Humans
Protein kinase A
Molecular Biology
030304 developmental biology
0303 health sciences
LAMP1
Tumor Necrosis Factor-alpha
Kinase
Chemistry
030302 biochemistry & molecular biology
Autophagosomes
Epithelial Cells
Cell Biology
Cell biology
Intestines
medicine.anatomical_structure
Receptor-Interacting Protein Serine-Threonine Kinases
biological phenomena, cell phenomena, and immunity
Lysosomes
Microtubule-Associated Proteins
Oligopeptides
Intracellular
Subjects
Details
- ISSN :
- 18733468 and 00145793
- Volume :
- 594
- Database :
- OpenAIRE
- Journal :
- FEBS Letters
- Accession number :
- edsair.doi.dedup.....ca31633ae325f6f9afa06d226a27d9a0