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. Author manuscript; available in PMC: 2013 Mar 1.
Published in final edited form as: Arthritis Rheum. 2012 Mar;64(3):718–728. doi: 10.1002/art.33407

Figure 6. Predicted role of 75SirT1 in chondrocyte survival.

Figure 6

Following TNFα stimulation caspase 8 dependant lysosomal permeability occurs. Lysosomal permeability exerts augmented levels of Cathepsin B in the cell cytoplasm and nucleus. Active Cathepsin B cleaves nuclear FLSirT1 to generate an inactive stable 75SirT1 fragment, which is exported via CRM1 to the cytoplasm (broken arrows). While in the Cytoplasm 75SirT1 interacts with Cytochrome C on the mitochondrial membrane to block downstream apoptososme assembly (broken arrows). Solid black arrows indicate the TNFα-Cathepsin B pathways through Bid activation. ALLN will block both Bid cleavage and 75SirT1 generation. The model may be relevant in-vivo for articular chondrocytes prone to develop OA (see SD-6).