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ATG9A prevents TNF cytotoxicity by an unconventional lysosomal targeting pathway.

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Title: ATG9A prevents TNF cytotoxicity by an unconventional lysosomal targeting pathway.
Authors: Huyghe, Jon, Priem, Dario, Van Hove, Lisette, Gilbert, Barbara, Fritsch, Jürgen, Yasuo Uchiyama, Hoste, Esther, van Loo, Geert, Bertrand, Mathieu J. M.
Source: Science (pre-March 2025). 12/16/2022, Vol. 378 Issue 6625, p1201-1207. 7p. 4 Color Photographs.
Subjects: Tumor necrosis factor regulation, Cell death, Immunology, Skin disease immunology, Apoptosis
Abstract: Cell death induced by tumor necrosis factor (TNF) can be beneficial during infection by helping to mount proper immune responses. However, TNF-induced death can also drive a variety of inflammatory pathologies. Protectives brakes, or cell-death checkpoints, normally repress TNF cytotoxicity to protect the organism from its potential detrimental consequences. Thus, although TNF can kill, this only occurs when one of the checkpoints is inactivated. Here, we describe a checkpoint that prevents apoptosis through the detoxification of the cytotoxic complex IIa that forms upon TNF sensing. We found that autophagy-related 9A (ATG9A) and 200kD FAK family kinase-interacting protein (FIP200) promote the degradation of this complex through a light chain 3 (LC3)–independent lysosomal targeting pathway. This detoxification mechanism was found to counteract TNF receptor 1 (TNFR1)–mediated embryonic lethality and inflammatory skin disease in mouse models. [ABSTRACT FROM AUTHOR]
Copyright of Science (pre-March 2025) is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Data: ATG9A prevents TNF cytotoxicity by an unconventional lysosomal targeting pathway.
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  Data: <searchLink fieldCode="AR" term="%22Huyghe%2C+Jon%22">Huyghe, Jon</searchLink><br /><searchLink fieldCode="AR" term="%22Priem%2C+Dario%22">Priem, Dario</searchLink><br /><searchLink fieldCode="AR" term="%22Van+Hove%2C+Lisette%22">Van Hove, Lisette</searchLink><br /><searchLink fieldCode="AR" term="%22Gilbert%2C+Barbara%22">Gilbert, Barbara</searchLink><br /><searchLink fieldCode="AR" term="%22Fritsch%2C+Jürgen%22">Fritsch, Jürgen</searchLink><br /><searchLink fieldCode="AR" term="%22Yasuo+Uchiyama%22">Yasuo Uchiyama</searchLink><br /><searchLink fieldCode="AR" term="%22Hoste%2C+Esther%22">Hoste, Esther</searchLink><br /><searchLink fieldCode="AR" term="%22van+Loo%2C+Geert%22">van Loo, Geert</searchLink><br /><searchLink fieldCode="AR" term="%22Bertrand%2C+Mathieu+J%2E+M%2E%22">Bertrand, Mathieu J. M.</searchLink>
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  Data: <searchLink fieldCode="JN" term="%22Science+%28pre-March+2025%29%22">Science (pre-March 2025)</searchLink>. 12/16/2022, Vol. 378 Issue 6625, p1201-1207. 7p. 4 Color Photographs.
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  Data: <searchLink fieldCode="DE" term="%22Tumor+necrosis+factor+regulation%22">Tumor necrosis factor regulation</searchLink><br /><searchLink fieldCode="DE" term="%22Cell+death%22">Cell death</searchLink><br /><searchLink fieldCode="DE" term="%22Immunology%22">Immunology</searchLink><br /><searchLink fieldCode="DE" term="%22Skin+disease+immunology%22">Skin disease immunology</searchLink><br /><searchLink fieldCode="DE" term="%22Apoptosis%22">Apoptosis</searchLink>
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  Data: Cell death induced by tumor necrosis factor (TNF) can be beneficial during infection by helping to mount proper immune responses. However, TNF-induced death can also drive a variety of inflammatory pathologies. Protectives brakes, or cell-death checkpoints, normally repress TNF cytotoxicity to protect the organism from its potential detrimental consequences. Thus, although TNF can kill, this only occurs when one of the checkpoints is inactivated. Here, we describe a checkpoint that prevents apoptosis through the detoxification of the cytotoxic complex IIa that forms upon TNF sensing. We found that autophagy-related 9A (ATG9A) and 200kD FAK family kinase-interacting protein (FIP200) promote the degradation of this complex through a light chain 3 (LC3)–independent lysosomal targeting pathway. This detoxification mechanism was found to counteract TNF receptor 1 (TNFR1)–mediated embryonic lethality and inflammatory skin disease in mouse models. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Science (pre-March 2025) is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=pbh&AN=160806418
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        Value: 10.1126/science.add6967
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      – SubjectFull: Immunology
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      – SubjectFull: Skin disease immunology
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              Text: 12/16/2022
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