Cited by 967Autophagy in Disease and TherapyInflammasome and immune disordersCellular transport and secretion

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Autophagy‐based unconventional secretory pathway for extracellular delivery of IL‐1β

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Dupont, Nicolas, Jiang, Shanya, Pilli, Manohar, Ornatowski, Wojciech, Bhattacharya, Dhruva, Deretic, Vojo·2011·The EMBO Journal

DOI 10.1038/emboj.2011.398PMC PMC3243609

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Abstract

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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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: Dupont, Nicolas
Jiang, Shanya
Pilli, Manohar
Ornatowski, Wojciech
Bhattacharya, Dhruva
Deretic, Vojo
Venue: The EMBO Journal
Publisher: Springer Science and Business Media LLC
Published: 2011-11-08
Volume: 30
Issue: 23
Pages: 4701-4711
ISSN: 0261-4189 (ISSN-L)
1460-2075
DOI: 10.1038/emboj.2011.398
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: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
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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Autophagy‐based unconventional secretory pathway for extracellular delivery of IL‐1β

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