PIPing on lysosome tubes

Abstract

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. Lysosomes, traditionally thought of as inert, terminal endocytic compartments, are in fact dynamic organelles. In addition to their function in degradation of cargo ranging from small vesicles to whole phagosomes and autophagosomes, they respond dynamically to extracellular ion fluxes, and they can generate potent intracellular calcium (and other ionic) signals (Saftig and Klumperman, 2009; Morgan et al , 2011; Shen et al , 2011). The cytoplasmic surface of the lysosome mediates the delivery of cargo‐containing vesicles and organelles via SNAREs and tethers, but is also a platform for TORC1 signalling and transcriptional regulation by TFEB (Settembre et al , 2011; Efeyan et al , 2012). The membrane of the lysosome, protected from the degradative enzymes contained in the lumen by highly glycosylated lysosomal membrane proteins (LAMPs, LIMPs, etc.), contains the machinery for its acidification (V‐ATPase), as well as a variety of transporters and channels for ions and amino …