Endosomal and lysosomal compartments

The endosomal and lysosomal compartments constitute a complex, dynamic network of membrane-bound organelles responsible for the internalization, sorting, and degradation of various macromolecules. These compartments are critical for the entry and trafficking of many viruses, which exploit the endocytic pathway to bypass the plasma membrane and reach the cytoplasm (Yamauchi & Helenius, 2013 [PMID: 23472851]). Within these organelles, the acidic environment and resident enzymes, such as cathepsins, facilitate the proteolytic cleavage and conformational changes of viral proteins required for membrane fusion (Simmons et al., 2005 [PMID: 16163351]). Therapeutic agents like hydroxychloroquine and chloroquine target this pathway by increasing the luminal pH, thereby inhibiting pH-dependent viral entry and replication (Wang et al., 2020 [PMID: 32075119]). Other experimental drugs, such as apilimod, target specific endosomal enzymes like PIKfyve to disrupt viral trafficking (Kang et al., 2020 [PMID: 32653444]). Beyond viral infection, the endolysosomal system is involved in the pathogenesis of cancer, neurodegenerative disorders, and lysosomal storage diseases (Boya, 2023 [PMID: 36804488]). Because these compartments are essential for cellular homeostasis, including nutrient signaling and protein turnover, pharmacological disruption can lead to significant safety concerns such as lysosomal toxicity and systemic side effects. Monitoring biomarkers like endosomal pH or cathepsin activity is often necessary to evaluate the efficacy and safety of drugs targeting this system.

Other names

Endolysosomal systemEndocytic pathwayVacuolar systemEndosomal-lysosomal system

Inhibition of endosomal acidification, inhibition of endosomal proteases, and disruption of viral-endosomal membrane fusion.