Figure 2.

Increased CD36 mediated FFA uptake and decreased ABCA1 expression mediated reduced cholesterol efflux lead to increased lipid accumulation and cause podocyte injury. Discoidin domain receptor 1 (DDR1) interacts with CD36 and induces CD36 activity. Increased CD36 activity in CKD mediates increased free fatty acid (FFA) uptake and triglyceride (TG) accumulation. Increased FFA uptake and TG lipolysis cause intracellular FFA overload to mitochondria, resulting in mitochondrial dysfunction. Cholesterol uptake from circulating LDL occurs via the LDL receptor. Esterified cholesterol accumulates in lipid droplets together with TGs. Decreased expression of ATP-binding cassette A1 (ABCA1)in podocytes in the setting of CKD leads to cholesterol accumulation, causing inefficient formation of the oxidative phosphorylation (OXPHOS) complex and increased oxidized cardiolipin accumulation in mitochondria, which leads to production of reactive oxygen species (ROS) and podocyte injury. CE, cholesteryl ester.