Figure 6.

Autophagy regulatory signaling pathways are involved in the pathological process of osteoarthritis/rheumatoid arthritis (OA/RA). (A) The AMPK/SIRT signaling pathway in OA chondrocytes regulates the mitochondrial function, mitophagy and mitochondrial biogenesis and defenses against excessive ROS mediated by superoxide dismutase 2/Parkin/ peroxisome proliferator-activated receptor gamma coactivator-1α (SOD2/Parkin/PGC-1α). (B) The phosphatidylinositol 3-kinase/protein kinase B/mTOR (PI3K/AKT/mTOR) signaling pathway. Cytokines or growth factors (such as insulin) activate AKT signaling via PI3K through binging to insulin receptor substrate protein (IRS). Activated AKT inhibits TSC1/2 complex activity on Rheb, stimulating the activation of mTOR, which deactivates the ULK1/mATG13/FIP200 protein kinase complex, autophagy regulator and Beclin-1 regulator to prevent autophagosome formation.