Fig. 2: The role of mitophagy in the pathogenesis of PDAC. | Cell Death Discovery

Fig. 2: The role of mitophagy in the pathogenesis of PDAC.

From: Mitophagy in pancreatic cancer: mechanistic insights and implications for novel therapeutic strategies

Fig. 2: The role of mitophagy in the pathogenesis of PDAC.

(Upper left) During pancreatic intraepithelial neoplasia (PanIN) progression, PINK1/Parkin-mediated mitophagy is suppressed, while receptor-mediated mitophagy (e.g., via NIX) is upregulated. This promotes tumor initiation and progression by enhancing redox homeostasis and driving a metabolic shift from oxidative phosphorylation (OXPHOS) to glycolysis. (Lower left) Cancer-associated fibroblasts (CAFs) undergo mitophagy and autophagy via the reverse Warburg effect. Cancer cell-induced oxidative stress triggers metabolic reprogramming in CAFs toward aerobic glycolysis, leading to the secretion of metabolites (e.g., lactate, ketones, proline) that support tumor growth. (Upper right) PINK1/PARK2 deletion upregulates PD-L1, and the ITGB4/BNIP3 complex promotes autophagic degradation of MHC-I, facilitating immune escape. (Lower right) ISG15-mediated ISGylation supports mitophagy in pancreatic cancer stem cells (CSCs), maintaining their metabolic plasticity and self-renewal capacity.

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