Autophagy and the immune function in aging - PubMed (original) (raw)
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Autophagy and the immune function in aging
Ana Maria Cuervo et al. Curr Opin Immunol. 2014 Aug.
Abstract
Just when you thought that you had heard it all about autophagy-the conserved cellular process that mediates turnover of cellular constituents in the lysosomes - studies keep coming out highlighting new types of autophagy, new functions for autophagy or even new autophagy-independent roles for the proteins associated with this process. The field of immunology has been riding the autophagic wave since the beginning of its revival; first due to its role in the host defense against pathogens, and more recently through the better understanding of the unique characteristics and functions of different autophagic pathways in immune cells. Here, we describe some of these new functions that are tightening the connection between autophagy and acquired or innate immunity and their malfunctioning with age.
Copyright © 2014 Elsevier Ltd. All rights reserved.
Figures
Figure 1. Schematic of the main autophagic pathways mammalian cells
Macroautophagy and chaperone-mediated autophagy deliver cytosolic cargo directly to lysosomes for degradation. In the case of endosomal microautophagy, cytosolic proteins are internalized in single membrane vesicles into late endosomes and undergo degradation in this compartment or in lysosomes upon endosome/lysosome fusion.
Figure 2. Autophagic functions in adaptive immunity
In dendritic cells, cytosolic proteins or those derived from intracellular pathogens can be delivered to be loaded into MHC-II through macroautophagy, CMA or endosomal microautophagy (e-microautophagy) to activate T cells. Whereas basal macroautophagy in T cells regulates organelle homeostasis (including mitochondria and endoplasmic reticulum), activation-induced macroautophagy in response to TCR engagement degrades cytosolic components to respond to increased metabolic demand and to modulate specific signaling pathways.
Figure 3. Age-related alteration in autophagy and its cellular consequences
The scheme depicted the most common mechanisms that contributed to malfunctioning of macroautophagy and chaperone-mediated autophagy with age. Boxes on the right summarized the main consequences that could follow autophagic malfunctioning with age separating those common to all cells (top) from those specific for immune cells (bottom).
References
- Levine B. Eating oneself and uninvited guests: autophagy-related pathways in cellular defense. Cell. 2005;120:159–162. - PubMed
- Codogno P, Mehrpour M, Proikas-Cezanne T. Canonical and non-canonical autophagy: variations on a common theme of self-eating? Nat Rev Mol Cell Biol. 2012;13:7–12. - PubMed
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