Journal Article

Lysosomes: fusion and function

Luzio, J. Paul, Pryor, Paul R., Bright, Nicholas A.

2007

Overview

Key Points Lysosomes are dynamic organelles that receive membrane traffic input from the secretory, endocytic, autophagic and phagocytic pathways. They can also fuse with the plasma membrane. Live-cell imaging has shown that lysosomes interact with late endosomes by 'kiss-and-run' events and by direct fusion. Fusion results in the formation of hybrid organelles, in which the degradation of endocytosed macromolecules occurs and from which lysosomes are re-formed. The use of yeast genetics and mammalian cell-free systems has identified much of the protein machinery that is involved in the delivery of macromolecules to lysosomes. The fusion of late endosomes with lysosomes involves tethering, the formation of trans -SNARE (soluble N -ethylmaleimide sensitive factor attachment protein receptor) complexes and phospholipid bilayer fusion. Conventional lysosomes may fuse with the plasma membrane in response to a rise in cytosolic Ca 2+ and can provide the additional membrane required for plasma-membrane wound repair. Specialized secretory lysosomes and lysosome-related organelles exist in some cell types. Lysosomes may also fuse with phagosomes and autophagosomes. Some phagocytosed pathogens can prevent or delay phagolysosome biogenesis; others escape their intracellular vacuole by degrading the phagosomal membrane and may evade autophagy or reside in autophagic compartments and delay the formation of autolysosomes. Upregulating autophagic pathways and the formation of autophagolysosomes provides the prospect of therapies for a range of proteinopathies including Huntington's disease and Parkinson's disease. Far from being a static organelle at the end of the endocytic pathway, the lysosome is capable of dynamically fusing with many organelles as well as the plasma membrane. The lysosome provides hydrolytic enzymes for the degradation of macromolecules, has secretory functions and is important for plasma membrane repair. Lysosomes are dynamic organelles that receive and degrade macromolecules from the secretory, endocytic, autophagic and phagocytic membrane-trafficking pathways. Live-cell imaging has shown that fusion with lysosomes occurs by both transient and full fusion events, and yeast genetics and mammalian cell-free systems have identified much of the protein machinery that coordinates these fusion events. Many pathogens that hijack the endocytic pathways to enter cells have evolved mechanisms to avoid being degraded by the lysosome. However, the function of lysosomes is not restricted to protein degradation: they also fuse with the plasma membrane during cell injury, as well as having more specialized secretory functions in some cell types.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: Analysis / Animals / Autophagy / Biochemistry / Biodegradation / Biological Evolution / Biomedical and Life Sciences / Cancer Research / Cell Biology / Cell hybridization / Cell-Free System - metabolism / Cell-Free System - microbiology / Cell-Free System - parasitology / Cell-Free System - ultrastructure / Cell-Free System - virology / Developmental Biology / Genetics / Humans / Life Sciences / Ligands / Lysosomes / Lysosomes - metabolism / Lysosomes - microbiology / Lysosomes - parasitology / Lysosomes - ultrastructure / Lysosomes - virology / Mammals / Membrane Fusion / Membranes / Microscopy / Pathogens / Phagocytosis / Physiological aspects / Proteins / Proteins - metabolism / review-article / Stem Cells / Yeast / Yeasts