Lysosomal Degradation of Proteins

J Fred Dice, Tufts University School of Medicine, Boston, Massachusetts, USA

Published online: July 2007

DOI: 10.1002/9780470015902.a0000646.pub2

Lysosomal enzymes and lysosomal membrane proteins are targeted to lysosomes by distinct mechanisms. Mutations that cause a reduction in activity of a lysosomal enzyme cause a variety of lysosomal storage diseases. Lysosomes are able to take up and degrade proteins by at least five different pathways, and their contribution to overall proteolysis depends on the cell type and its physiological status. Recent studies have begun to define the molecular mechanisms of macroautophagy, microautophagy, and chaperone-mediated autophagy.

Keywords: lysosome biogenesis; lysosomal enzymes; macroautophagy; microautophagy; chaperone-mediated autophagy

Figure 1. Lysosomes can internalize and degrade proteins by a variety of mechanisms. See the text for a description of the pathways of endocytosis, exocytosis, macroautophagy, microautophagy, and chaperone-mediated autophagy. END, endosome; RV, recycling vesicles; SV, secretory vesicles; L, lysosomes; AV, autophagic vacuoles; AP, autophagosomes; M, mitochondrion; ER, endoplasmic reticulum; N, nucleus; G, Golgi.
Figure 2. Two conjugation systems are required for macroautophagy. Two proteins are covalently conjugated (top), and phosphatidyl-ethanolamine (PE) is conjugated to Atg8p (bottom). Both processes utilize the same ubiquitin activating protein (E1) but different ubiquitin carrier proteins (E2 s).
Figure 3. Microautophagy of peroxisomes in Pichia pastoris. Stages 0 through 4 are shown along with mutations that block microautophagy at the stages indicated. N, nucleus; V, vacuole.
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    book Klionsky DJ (ed.) (2004) Autophagy. Austin, TX: Landes Bioscience, Inc.
    book Saftig P (2005) Lysosomes. Austin, TX: Landes Bioscience, Inc.

Related Sub-Topics:

Basic Cell Biology, Protein, RNA and DNA | Cell Compartments and Cellular Organelles | Protein Degradation | Proteins: Structure, Function, Metabolism | Enzymes: Structure and Action Mechanism
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Article Title: Lysosomal Degradation of Proteins
 
How to Cite close
Dice, J Fred(Jul 2007) Lysosomal Degradation of Proteins. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000646.pub2]