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Most of these studies emphasized the role of the mitochondria in this process. However, the engagement of other organelles is less known. Particularly, the role of lysosomes and their proteolytic system, which participates in apoptotic cell death, is still unclear. The aim of this study was to investigate the role of lysosomal cathepsins on molecular signaling in MD\u2010induced apoptosis in U937 cells. MD treatment induced translocation of cysteine cathepsins B, C, and S, and aspartic cathepsin D. Once in the cytosol, some cathepsins cleaved the proapoptotic molecule, Bid, in a process that was completely prevented by E64d, a general inhibitor of cysteine cathepsins, and partially prevented by the pancaspase inhibitor, z\u2010VAD\u2010fmk. Upon loss of the mitochondrial membrane potential, apoptosome activation led to caspase\u20109 processing, activation of caspase\u20103\u2010like caspases, and poly (ADP\u2010ribose) polymerase cleavage. Notably, the endogenous protein inhibitor, stefin B, was degraded by cathepsin D and caspases. This process was prevented by z\u2010VAD\u2010fmk, and partially by pepstatin A\u2010penetratin. These findings suggest that the cleaved Bid protein acts as an amplifier of apoptotic signaling through mitochondria, thus enhancing the activity of cysteine cathepsins following stefin B degradation.<\/jats:p>","DOI":"10.1002\/jcb.28356","type":"journal-article","created":{"date-parts":[[2019,1,17]],"date-time":"2019-01-17T04:34:24Z","timestamp":1547699664000},"page":"10662-10669","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Menadione\u2010induced apoptosis in U937 cells involves Bid cleavage and stefin B degradation"],"prefix":"10.1002","volume":"120","author":[{"given":"Janja","family":"Bo\u017ei\u010d","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular and Structural Biology Jo\u017eef Stefan Institute Ljubljana Slovenia"},{"name":"Jo\u017eef Stefan International Postgraduate School Ljubljana 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