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.