ATG9A prevents TNF cytotoxicity by an unconventional lysosomal targeting pathway.
- Author
- Jon Huyghe (UGent) , Dario Priem (UGent) , Lisette Van Hove, Barbara Gilbert (UGent) , J Fritsch, Y Uchiyama, Esther Hoste (UGent) , Geert van Loo (UGent) and Mathieu Bertrand (UGent)
- Organization
- Project
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- Autophagy in inflammation and inflammatory disorders (ATLANTIS), from basic insights to experimental therapy
- Study of RIPK1 involvement and regulation in inflammatory and infectious diseases
- Cell Death Regulation and Role in Infection and Inflammatory Diseases
- Cell death activity regulation in inflammation and cancer
- 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.
- Keywords
- DEFICIENCY, PHOSPHORYLATION, IMMUNODEFICIENCY, DEATH, AUTOPHAGY, LIVER DEGENERATION, EMBRYONIC LETHALITY, NF-KAPPA-B
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-01GPDNEWVPR90SFCDNE3EBJ1BK
- MLA
- Huyghe, Jon, et al. “ATG9A Prevents TNF Cytotoxicity by an Unconventional Lysosomal Targeting Pathway.” SCIENCE, vol. 378, no. 6625, 2022, pp. 1201–07, doi:10.1126/science.add6967.
- APA
- Huyghe, J., Priem, D., Van Hove, L., Gilbert, B., Fritsch, J., Uchiyama, Y., … Bertrand, M. (2022). ATG9A prevents TNF cytotoxicity by an unconventional lysosomal targeting pathway. SCIENCE, 378(6625), 1201–1207. https://doi.org/10.1126/science.add6967
- Chicago author-date
- Huyghe, Jon, Dario Priem, Lisette Van Hove, Barbara Gilbert, J Fritsch, Y Uchiyama, Esther Hoste, Geert van Loo, and Mathieu Bertrand. 2022. “ATG9A Prevents TNF Cytotoxicity by an Unconventional Lysosomal Targeting Pathway.” SCIENCE 378 (6625): 1201–7. https://doi.org/10.1126/science.add6967.
- Chicago author-date (all authors)
- Huyghe, Jon, Dario Priem, Lisette Van Hove, Barbara Gilbert, J Fritsch, Y Uchiyama, Esther Hoste, Geert van Loo, and Mathieu Bertrand. 2022. “ATG9A Prevents TNF Cytotoxicity by an Unconventional Lysosomal Targeting Pathway.” SCIENCE 378 (6625): 1201–1207. doi:10.1126/science.add6967.
- Vancouver
- 1.Huyghe J, Priem D, Van Hove L, Gilbert B, Fritsch J, Uchiyama Y, et al. ATG9A prevents TNF cytotoxicity by an unconventional lysosomal targeting pathway. SCIENCE. 2022;378(6625):1201–7.
- IEEE
- [1]J. Huyghe et al., “ATG9A prevents TNF cytotoxicity by an unconventional lysosomal targeting pathway.,” SCIENCE, vol. 378, no. 6625, pp. 1201–1207, 2022.
@article{01GPDNEWVPR90SFCDNE3EBJ1BK,
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.}},
author = {{Huyghe, Jon and Priem, Dario and Van Hove, Lisette and Gilbert, Barbara and Fritsch, J and Uchiyama, Y and Hoste, Esther and van Loo, Geert and Bertrand, Mathieu}},
issn = {{0036-8075}},
journal = {{SCIENCE}},
keywords = {{DEFICIENCY,PHOSPHORYLATION,IMMUNODEFICIENCY,DEATH,AUTOPHAGY,LIVER DEGENERATION,EMBRYONIC LETHALITY,NF-KAPPA-B}},
language = {{eng}},
number = {{6625}},
pages = {{1201--1207}},
title = {{ATG9A prevents TNF cytotoxicity by an unconventional lysosomal targeting pathway.}},
url = {{http://doi.org/10.1126/science.add6967}},
volume = {{378}},
year = {{2022}},
}
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