Lysosomes relax in the cellular suburbs

Abstract

Lysosomes support cellular homeostasis by degrading macromolecules and recycling nutrients. In this issue, Johnson et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201507112) reveal a heterogeneity in lysosomal pH and degradative ability that correlates with lysosome subcellular localization, raising questions about the functional implications and mechanisms underlying these observations.

Figure 1.

Overview of the relationship between lysosome subcellular position and function. (A) Lysosome distribution in a HeLa cell revealed by confocal imaging of the lysosomal marker LAMP1 (red) and nuclear staining with DAPI (blue). This image represents a maximum projection of two confocal sections. Image courtesy of A. Roczniak-Ferguson (Yale University, New Haven, CT). Bar, 10 µm. (B) Schematic diagram of the impact of subcellular localization on the functional properties of lysosomes. The GTPase effector pairs Rab7-RILP, Arl8-SKIP, and Rab7-FYCO control the localization of lysosomes within the cell. Peripheral lysosomes (yellow circles with orange borders) display reduced acidification caused by an increased passive leak of protons and reduced V-ATPase activity. This lysosome population displays reduced Rab7 density, resulting in decreased recruitment of the Rab7 effector RILP, which could both negatively impact the activity of the V-ATPase and limit dynein-mediated transport back toward the cell center. Peripheral lysosomes also exhibit reduced access to material from the secretory pathway. In contrast, perinuclear lysosomes (green circles with red borders) have a more acidic pH and higher Rab7-RILP density. Experimental movement of lysosomes from the perinuclear region to the cell periphery is associated with reduced acidification and impaired proteolytic activity.