دورية أكاديمية
Discovery of SQSTM1/p62-dependent P-bodies that regulate the NLRP3 inflammasome
| العنوان: | Discovery of SQSTM1/p62-dependent P-bodies that regulate the NLRP3 inflammasome |
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| المؤلفون: | Barrow, ER, Valionyte, E, Baxter, CR, Yang, Y, Herath, S, O’Connell, WA, Lopatecka, J, Strachan, A, Woznica, W, Stephenson, HN, Fejer, G, Sharma, V, Lu, B, Luo, S |
| بيانات النشر: | Elsevier BV United States |
| سنة النشر: | 2024 |
| المجموعة: | PEARL (Plymouth Electronic Archiv & ResearchLibrary, Plymouth University) |
| مصطلحات موضوعية: | ASC/PYCARD, CP: Molecular biology, LLPS, NLRP3 inflammasome, P-bodies, RNP granules, SQSTM1/p62, autophagy, liquid-liquid phase separation, stress granules, Humans, Inflammasomes, NLR Family, Pyrin Domain-Containing 3 Protein, Sequestosome-1 Protein, Processing Bodies, Inflammation |
| الوصف: | Autophagy and ribonucleoprotein granules, such as P-bodies (PBs) and stress granules, represent vital stress responses to maintain cellular homeostasis. SQSTM1/p62 phase-separated droplets are known to play critical roles in selective autophagy; however, it is unknown whether p62 can exist as another form in addition to its autophagic droplets. Here, we found that, under stress conditions, including proteotoxicity, endotoxicity, and oxidation, autophagic p62 droplets are transformed to a type of enlarged PBs, termed p62-dependent P-bodies (pd-PBs). p62 phase separation is essential for the nucleation of pd-PBs. Mechanistically, pd-PBs are triggered by enhanced p62 droplet formation upon stress stimulation through the interactions between p62 and DDX6, a DEAD-box ATPase. Functionally, pd-PBs recruit the NLRP3 inflammasome adaptor ASC to assemble the NLRP3 inflammasome and induce inflammation-associated cytotoxicity. Our study shows that p62 droplet-to-PB transformation acts as a stress response to activate the NLRP3 inflammasome process, suggesting that persistent pd-PBs lead to NLRP3-dependent inflammation toxicity. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | 113935-113935; Print-Electronic; application/pdf |
| اللغة: | English |
| تدمد: | 2211-1247 |
| العلاقة: | E-ISSN:2211-1247; 113935; https://pearl.plymouth.ac.uk/handle/10026.1/22374Test |
| DOI: | 10.1016/j.celrep.2024.113935 |
| الإتاحة: | https://doi.org/10.1016/j.celrep.2024.113935Test https://pearl.plymouth.ac.uk/handle/10026.1/22374Test |
| رقم الانضمام: | edsbas.C51F6A3 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 22111247 |
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| DOI: | 10.1016/j.celrep.2024.113935 |