Behind every smile there's teeth: Cathepsin B's function in health and disease with a kidney view

• Published in: Biochimica et biophysica acta. Molecular cell research 2022-04, Vol.1869 (4), p.119190-119190, Article 119190
• Main Authors: Saudenova, Makhabbat, Promnitz, Jessica, Ohrenschall, Gerrit, Himmerkus, Nina, Böttner, Martina, Kunke, Madlen, Bleich, Markus, Theilig, Franziska
• Format: Article
• Language: English
• Subjects: Animals; Cathepsin B - chemistry; Cathepsin B - metabolism; Diabetes Mellitus - metabolism; Diabetes Mellitus - pathology; Humans; Inflammasomes - metabolism; Kidney - metabolism; Kidney Diseases - metabolism; Kidney Diseases - pathology; Lysosomes - metabolism; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism
• ISSN: 0167-4889; 1879-2596
• DOI: 10.1016/j.bbamcr.2021.119190

Cathepsin B (CatB) is a very abundant lysosomal protease with endo- and carboxydipeptidase activities and even ligase features. In this review, we will provide a general characterization of CatB and describe structure, structure-derived properties and location-dependent proteolytic actions. We depict CatB action within lysosome and its important roles in lysosomal biogenesis, lysosomal homeostasis and autophagy rendering this protease a key player in orchestrating lysosomal functions. Lysosomal leakage and subsequent escape of CatB into the cytosol lead to harmful actions, e.g. the role in activating the NLPR3 inflammasome, affecting immune responses and cell death. The second focus of this review addresses CatB functions in the kidney, i.e. the glomerulus, the proximal tubule and collecting duct with strong emphasis of its role in pathology of the respective segment. Finally, observations regarding CatB functions that need to be considered in cell culture will be discussed. In conclusion, CatB a physiologically important molecule may, upon aberrant expression in different cellular context, become a harmful player effectively showing its teeth behind its smile. •the cysteine protease CatB plays important roles in lysosomal function•CatB affects inflammatory responses by inflammasome activation•CatB is a key player in renal diseases, affecting the glomerular-, proximal tubule and collecting duct cells•CatB expression in vivo and in cultured cells deserves critical evaluation•In degenerative disorders, CatB is reduced in lysosomes causing lysosomal dysfunction, impaired autophagy and ECM accumulation in the extracellular space. In inflammatory disorders, lysosomal membrane perforation cause CatB release into the cytosol, triggering inflammasome activation and promoting cell death.