Damage-associated molecular patterns (DAMPs) are molecules within living cells that are released when cell membranes are ruptured. Although DAMPs have physiological functions inside the cell, once DAMPs are released extracellularly, they elicit various biological responses, including inflammation, proliferation, tissue damage, and tissue repair, in a context-dependent manner. In past decades, it was assumed that the release of DAMPs was induced by a membrane rupture, caused by passive ATP depletion, or by chemical or mechanical damage to the membrane. However, that concept has been challenged by recent advancements in understanding the regulation of cell death. Necroptosis is a form of regulated cell death, where cells show necrotic morphology. Necroptosis is triggered by death receptors, toll-like receptors, and some viral infections. The membrane rupture is executed by the mixed lineage-like kinase domain-like pseudokinase (MLKL), which forms oligomers that translocate to the plasma membrane during necroptosis. Although the causal relationship between MLKL function and membrane rupture has been extensively investigated, the detailed molecular mechanisms by which oligomerized MLKL induces membrane rupture are not fully understood. This review summarizes recent advances in understanding how MLKL regulates DAMP release and new technologies for visualizing DAMP release at single-cell resolution.
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March 2022
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Deletion of Slc6a14 reduces the proliferation capacity and the desmoplastic reaction in the KPC mice. Immunohistochemical analysis showing staining of CK19 (top), Ki67 (second), α-SMA (third) and Masson’s Trichrome (bottom) in KPC (left) and KPCS (right) pancreatic tumour sections. Scale bar: 100 μm.
Review Article|
March 16 2022
Regulation of the release of damage-associated molecular patterns from necroptotic cells
In Collection
Cell death and survival
Hiroyasu Nakano
;
Department of Biochemistry, Toho University School Medicine, 5-21-16 Omori-Nishi, Ota-ku, Tokyo 143-8540, Japan
Correspondence: Hiroyasu Nakano (hiroyasu.nakano@med.toho-u.ac.jp)
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Shin Murai;
Shin Murai
Department of Biochemistry, Toho University School Medicine, 5-21-16 Omori-Nishi, Ota-ku, Tokyo 143-8540, Japan
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Kenta Moriwaki
Kenta Moriwaki
Department of Biochemistry, Toho University School Medicine, 5-21-16 Omori-Nishi, Ota-ku, Tokyo 143-8540, Japan
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Publisher: Portland Press Ltd
Received:
February 02 2022
Revision Received:
February 23 2022
Accepted:
February 25 2022
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2022 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2022
Biochem J (2022) 479 (5): 677–685.
Article history
Received:
February 02 2022
Revision Received:
February 23 2022
Accepted:
February 25 2022
Citation
Hiroyasu Nakano, Shin Murai, Kenta Moriwaki; Regulation of the release of damage-associated molecular patterns from necroptotic cells. Biochem J 18 March 2022; 479 (5): 677–685. doi: https://doi.org/10.1042/BCJ20210604
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