Autophagy and cancer

Figure 2 Schematic illustration of differential regulation of mitophagy participating in the progression of pancreatic cancer. Numbers in parentheses indicate successive mitophagy processes that are interrelated. A: During the early stages of pancreatic cancer: (1) BNIP3 is transcribed; (2) translated and inserted into mitochondria membrane; (3) Active BNIP3 tethers mitochondria to the phagophore through its interaction with LC-3;(4) Mitochondria are therefore selectively engulfed in the autophagosome and degraded by the lysosome. In this way, mitochondria-induced ROS production is limited and genome stability is preserved; B: In the later stages of pancreatic cancer: (1) BNIP3 gene is silenced; (2) The absence of BNIP3 on the mitochondrial outer membrane will prevent the process of selective targeting of mitochondria to the autophagy machinery; (3) Accumulation of damaged mitochondria will result in elevated production of ROS and increased genome instability, which further contributes to the progression of cancer.