Journal
JOURNAL OF INNATE IMMUNITY
Volume 5, Issue 5, Pages 471-479Publisher
KARGER
DOI: 10.1159/000346707
Keywords
Autophagy; Alarmins; Inflammasome; Calpain
Categories
Funding
- National Institutes of Health Colitis Foundation of America [AI042999, AI069345, ARRA RC1AI086845, CCFA2053]
- Bill and Melinda Gates Grand Challenge Explorations grant
- NCRR
- National Center for Advancing Translational Sciences NIH [UL1 TR000041]
- [3R01AI042999-13S1]
- NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES [UL1TR000041] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI042999, RC1AI086845, R01AI069345] Funding Source: NIH RePORTER
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Autophagy (macroautophagy) is often defined as a degradative process and a tributary of the lysosomal pathway. In this context, autophagy carries out cytoplasmic quality control and nutritional functions by removing defunct or disused organelles, particulate targets and invading microbes, and by bulk digestion of the cytoplasm. However, recent studies indicate that autophagy surprisingly affects multiple secretory pathways. Autophagy participates in extracellular delivery of a number of cytosolic proteins that do not enter the conventional secretory pathway via the Golgi apparatus but are instead unconventionally secreted directly from the cytosol. In mammalian cells, a prototypical example of this manifestation of autophagy is the unconventional secretion of a major proinflammatory cytokine, IL-1 beta. This review examines the concept of secretory autophagy and compares and contrasts the role of autophagy in the secretion of IL-1 alpha and IL-1 beta. Although IL-1 alpha and IL-1 beta have closely related extracellular inflammatory functions, they differ in intracellular activation, secretory mechanisms and how they are affected by autophagy. This example indicates that the role of autophagy in secretion is more complex, at least in mammalian cells, than the simplistic view that autophagosomes provide carriers for unconventional secretion of cytosolic proteins. Copyright (c) 2013 S. Karger AG, Basel
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