New Insights in the Endo-Lysosomal System Using Correlative Light and Electron Microscopy

Abstract

The endo-lysosomal system is a complex organelle network wherein the endocytosed cargo is either recycled or degraded for metabolic re-use. This intricate system consists of many distinct organelles and significant insights about the molecular and functional parameters, transport and maturation dynamics, interactions, and regulatory mechanisms have emerged in the last decade. Particularly, correlative light and electron microscopy (CLEM) methods enable novel advancements in our understanding. CLEM combines the strengths of light microscopy, mainly its fluorescence and live-cell imaging, with the strengths of electron microscopy, high-resolution ultrastructure, within the same cells. In this review, we provide an overview of recent advances in CLEM methods and their applications within the endo-lysosomal system over the last decade and summarize the findings per organelle. Recent, CLEM-based research showed early endosomes compartmentalize in two distinct domains, facilitating the recycling and the degradative pathways. Generic early endosome protein markers are not completely specific for early endosomes. Furthermore, calcium concentration is enriched in late endosomes. Lysosome motility is dependent on the number of contact sites with other organelles. Finally, the degradative capacity of endolysosomes and lysosomes with respect to their ultrastructural characteristics is questioned.