endolysosomal

Endolysosomal refers to the cellular system that degrades and recycles macromolecules delivered by endocytosis, autophagy, and phagocytosis. It encompasses endosomes, lysosomes, and the degradative compartments that arise from their maturation and fusion. The endolysosome describes a hybrid organelle formed when late endosomes fuse with lysosomes, containing hydrolytic enzymes and an acidic lumen to break down proteins, lipids, and nucleic acids.

Maturation and trafficking within the endolysosomal system start with cargo entering through the plasma membrane and reaching early endosomes, marked by Rab5 and phosphatidylinositol 3-phosphate. These compartments mature into late endosomes as Rab7 replaces Rab5 and lysosomal membrane proteins are acquired. Late endosomes then fuse with lysosomes to form endolysosomes, where hydrolases act on substrates. The lumen is acidified by V-ATPases, creating an optimal environment for enzymatic activity.

Functions of the endolysosomal system extend beyond bulk degradation. It participates in receptor recycling, cholesterol and lipid trafficking, and antigen processing for immune responses. It also contributes to cellular signaling, including nutrient sensing by mTORC1 at lysosomal membranes. Molecular machinery such as ESCRT complexes, SNAREs, and Rab GTPases coordinates cargo sorting, multivesicular body formation, and membrane fusion events.

Clinical relevance arises from dysfunctions in endolysosomal trafficking and degradation. Lysosomal storage disorders, including Pompe disease, Niemann-Pick, and Gaucher disease, reflect impaired enzymatic activity or trafficking. The endolysosomal axis is also linked to neurodegenerative and immune disorders. Therapeutic approaches include enzyme replacement therapy, pharmacological chaperones, and gene therapy, with ongoing research into improving delivery and correcting underlying trafficking defects.