Abstract

In eukaryotic cells, lysosomes are distributed in the cytoplasm as individual membrane-bound compartments to degrade macromolecules and to control cellular metabolism. A fundamental yet unanswered question is whether and, if so, how individual lysosomes are spatially organized so that their functions can be coordinated and integrated to meet changing needs of cells. To address this question, we analyze their collective behavior in cultured cells using spatial statistical techniques. We find that in single cells, lysosomes maintain nonrandom, stable, yet distinct spatial distributions, which are mediated by the coordinated effects of the cytoskeleton and lysosomal biogenesis on different lysosomal subpopulations. Furthermore, we find that throughout the intracellular space, lysosomes form dynamic clusters that substantially increase their interactions with endosomes. Together, our findings reveal the spatial organization of lysosomes at the whole-cell scale and provide new insights into how organelle interactions are mediated and regulated over the entire intracellular space.\n\nHighlightsO_LILysosomes maintain stable yet distinct spatial distributions in single cells\nC_LIO_LIThe cytoskeleton and lysosomal biogenesis mediate stable lysosomal distributions\nC_LIO_LILysosomes form dynamic clusters that promote their interactions with endosomes\nC_LIO_LITwo subpopulations of lysosomes jointly mediate formation of lysosomal clusters\nC_LI\n\neTOC BlurbLysosomes are spatially organized at the whole-cell scale and form dynamic clusters that promote their interactions with endosomes.