Figure 2

Schematic illustration of the molecular processes leading to apoptosis in renal proximal tubular epithelial cells. So-called death receptors such as Fas, TNF receptor-1 (TNFR-1), or the TNF-related apoptosis-inducing ligand (TRAIL) receptors bind with extracellular ligands to activate downstream activator caspases [78]. This process is usually mediated by the FADD (Fas-associated protein with death domain) receptor, and ultimately activates caspase-3 - the effector molecule. Within the cell, the intrinsic pathway is initiated via cellular stresses: reactive oxygen species (ROS), nitric oxide, decreased ATP, or cell-cell/cell-matrix perturbations [95]. In response to those stresses, BAX migrates into the mitochondria via activation from BH3-only proteins within the Bcl-2 family [96]. Once they have entered the mitochondria, BAX and other pro-apoptotic proteins form pores within the mitochondrial wall, allowing for the release of cytochrome c, which triggers caspase-dependent and -independent pathways [95].