The DOI matches its Crossref record; 68 of the 68 references it cites were found in a registry or an index.
Autophagy‐based unconventional secretory pathway for extracellular delivery of IL‐1β
Open accessAbstract
Autophagy controls the quality and quantity of the eukaryotic cytoplasm while performing two evolutionarily highly conserved functions: cell-autonomous provision of energy and nutrients by cytosol autodigestion during starvation, and removal of defunct organelles and large aggregates exceeding the capacity of other cellular degradative systems. In contrast to these autodigestive processes, autophagy in yeast has additional, biogenesis functions. However, no equivalent biosynthetic roles have been described for autophagy in mammals. Here, we show that in mammalian cells, autophagy has a hitherto unappreciated positive contribution to the biogenesis and secretion of the proinflammatory cytokine IL-1β via an export pathway that depends on Atg5, inflammasome, at least one of the two mammalian Golgi reassembly stacking protein (GRASP) paralogues, GRASP55 (GORASP2) and Rab8a. This process, which is a type of unconventional secretion, expands the functional manifestations of autophagy beyond autodigestive and quality control roles in mammals. It enables a subset of cytosolic proteins devoid of signal peptide sequences, and thus unable to access the conventional pathway through the ER, to enter an autophagy-based secretory pathway facilitating their exit from the cytoplasm.
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“Autophagy has also been recognized to mediate the secretion of proteins (34) – such as IL-1β and IL-18 (35, 36) – that would otherwise not enter the classical secretory pathway due to lack of a leader peptide.”
From Macrophage Cytokines: Involvement in Immunity and Infectious Diseases (2014) · cites this paper as [35]
In the citing paper
“IL-18 trafficking is similar to that of IL-1β, with secretory autophagy also playing a major role in its release (35, 36).”
From Macrophage Cytokines: Involvement in Immunity and Infectious Diseases (2014) · cites this paper as [35]
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Cites
Repertoires of Autophagy in the Pathogenesis of Ocular Diseases
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AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1
Kim, J., Kundu, M., Viollet, B., & Guan, K.-L. (2011) · Nature Cell Biology · doi:10.1038/ncb2152 · Cited by 7,227
Autophagy fights disease through cellular self-digestion
Mizushima, N., Levine, B., Cuervo, A. M., & Klionsky, D. J. (2008) · Nature · doi:10.1038/nature06639 · Cited by 6,452
A role for mitochondria in nlrp3 inflammasome activation
Zhou, R., Yazdi, A. S., Menu, P., & Tschopp, J. (2011) · Nature · doi:10.1038/nature09663 · Cited by 5,602
Gout-associated uric acid crystals activate the NALP3 inflammasome
Martinon, F., Pétrilli, V., Mayor, A., Tardivel, A., & Tschopp, J. (2006) · Nature · doi:10.1038/nature04516 · Cited by 5,326
Methods in Mammalian Autophagy Research
Mizushima, N., Yoshimori, T., & Levine, B. (2010) · Cell · doi:10.1016/j.cell.2010.01.028 · Cited by 4,497
Antimicrobial Autophagy: A Conserved Innate Immune Response in Drosophila
Moy, R. H., & Cherry, S. R. (2013) · Journal of Innate Immunity · doi:10.1159/000350326 · Cited by 3,551
Autophagy and the Integrated Stress Response
Kroemer, G., Mariño, G., & Levine, B. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.09.023 · Cited by 3,506
Autophagy in immunity and inflammation
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Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).
Klionsky, D. J., Abdelmohsen, K., Abe, A., Abedin, M. J., Abeliovich, H., Acevedo Arozena, A., Adachi, H., Adams, C. M., Adams, P. D., Adeli, K., et al. (2016) · Autophagy · doi:10.1080/15548627.2015.1100356 · Cited by 5,894
Autophagy and Viruses: Adversaries or Allies?
Dong, X., & Levine, B. (2013) · Journal of Innate Immunity · doi:10.1159/000346388 · Cited by 4,444
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 1
Klionsky, D. J., Abdel-Aziz, A. K., Abdelfatah, S., Abdellatif, M., Abdoli, A., Abel, S., Abeliovich, H., Abildgaard, M. H., Abudu, Y. P., Acevedo-Arozena, A., et al. (2021) · Autophagy · doi:10.1080/15548627.2020.1797280 · Cited by 2,897
Self-citationBiological Functions of Autophagy Genes: A Disease Perspective
Levine, B., & Kroemer, G. (2019) · Cell · doi:10.1016/j.cell.2018.09.048 · Cited by 2,832
Macrophage Cytokines: Involvement in Immunity and Infectious Diseases
Arango Duque, G., & Descoteaux, A. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00491 · Cited by 2,708
“Lack of fever induction may be explained by the fact that IL-18 signals through the MAPK p38 pathway instead of the NF-κB pathway, which is used by IL-1β (54).”
BackgroundInfluential
Metadata
- Authors
- Dupont, N., Jiang, S., Pilli, M., Ornatowski, W., Bhattacharya, D., & Deretic, V.
- Affiliations
- University of New Mexico Health Sciences Center (US)
- University of New Mexico (US)
- Corresponding author
- Deretic, Vojo
- ORCID
- Venue
- The EMBO Journal
- Published
- 2011-11-08
- Volume
- 30
- Issue
- 23
- Pages
- 4701-4711
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC3243609
- OpenAlex
- W2109070574
- Cited by
- 967
- References
- 68
- Citations by year
- 2026: 41 · 2025: 68 · 2024: 63 · 2023: 54 · 2022: 96 · 2021: 73 · 2020: 86 · 2019: 55 · 2018: 68 · 2017: 66 · 2016: 77 · 2015: 50 · 2014: 56 · 2013: 66 · 2012: 45
- FWCI
- 40.73
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The EMBO Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (AI042999)
- National Institute of Allergy and Infectious Diseases (RC1AI086845, R01AI042999, R01AI069345, R37AI042999)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- autophagy, unconventional secretion, IL-1β, proinflammatory cytokine secretion, ATG5, inflammasome, GRASP55, Rab8a
- MeSH terms
- Autophagy-Related Protein 5, Animals, Autophagy, Carrier Proteins, Cells, Cultured, Luminescent Proteins, Macrophages, Membrane Proteins, Microtubule-Associated Proteins, Nigericin, Protein Processing, Post-Translational, Macrolides, Interleukin-18, rab GTP-Binding Proteins, Protein Transport, HMGB1 Protein, Intracellular Signaling Peptides and Proteins, Mice, Interleukin-1beta, Secretory Pathway, Inflammasomes
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