PIPing on lysosome tubes

Abstract

EMBO J (2013) 32, 324–339 doi:; DOI: 10.1038/emboj.2012.341; published online December 21 2012

The role of lysosomes in important cellular responses, including phagocytosis, cell surface repair, and autophagy underlies a number of human diseases. Furthermore, the role of the lysosomal surface in TORC1 signalling has revealed unexpected properties of these organelles. In this issue, Sridhar et al (2013) uncover an important role for PI(4)P for lysosome function under normal nutrient conditions and after prolonged nutrient deprivation. Ana Maria Cuervo, the late Dennis Shields, and colleagues (Sridhar et al, 2013) conclude that PI4 kinase IIIβ on the surface of the lysosome controls the fidelity of sorting from the lysosome, and is required for autophagic lysosome reformation (ALR). These novel findings provide important insights into the complexities of the lipid composition of the lysosome, and how these lipids may control lysosome function.

Figure 1

Two phosphoinositide cycles regulate aspects of lysosome function. (A) Pathway of synthesis and consumption of PI3P, PI(3,5)P₂, PI(4)P and PI(4,5)P₂ from PA via PI. The relative abundance of the various lipid species is shown, alongside the main enzymes responsible for their synthesis and consumption. (B) Stress responses of lysosomes following extracellular or intracellular challenge are regulated in part by PI3P and PI(3,5)P₂, with the former involved in fusion with other organelles and the latter in regulation of ion channels (shown in green). A second phosphoinositide cycle dependent on PI(4)P and PI(4,5)P₂ was uncovered in the paper by Sridhar et al (2013), which regulates traffic from the lysosomes either in the form of vesicles or tubules (shown in blue, PI(4)P favouring vesicular intermediates). Recent work by Yu and colleagues has also suggested that these lipids regulate lysosome reformation during enhanced flux, also thought to proceed via a tubular intermediate favouring PI(4,5)P₂ (shown in blue).