Lysosomal Degradation of Proteins

Abstract

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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Further Reading

Clague MJ and Hammond DE (2006) Membrane traffic: catching the lysosome express. Current Biology 16: R416–R418.

Dice JF (2000) Lysosomal Pathways of Protein Degradation. Austin, TX: Landes Bioscience, Inc.

Holtzman E (1989) Lysosomes. New York and London: Plenum Press.

Janvier K and Bonaficino JS (2005) Role of the endocytic machinery in sorting of lysosomal‐associated proteins. Molecular Biology of the Cell 16: 4231–4242.

Klionsky DJ (ed.) (2004) Autophagy. Austin, TX: Landes Bioscience, Inc.

Saftig P (2005) Lysosomes. Austin, TX: Landes Bioscience, Inc.

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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]