PLOS ONE · 11 authors, 6 centres
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This preclinical study used a mouse pancreatic β-cell line and 3D organoids to investigate a cellular pathway under diabetic stress. The central finding is that STZ-induced stress increases mitochondrial ROS via Plk3, leading to Parkin recruitment and mitophagy that inhibits β-cell growth and insulin secretion, while FOXO3A negatively regulates this process.
The study investigated mechanisms of mitophagy in pancreatic β-cells under diabetic stress using Beta TC-6 cells and a 3D organoid *ex vivo* model. The authors found that streptozotocin (STZ) stress induced mitochondrial recruitment of Parkin via Plk3-mediated mitochondrial ROS generation, a process that inhibited pancreatic cell growth and insulin secretion. They identified that FOXO3A acts as a negative regulator of this pathway by inhibiting Plk3. Antioxidants (NAC, natural COA water) were shown to block mitochondrial ROS and subsequent Parkin recruitment. In the 3D model, both ROS inhibition and mitophagy inhibition (via 3-MA or Parkin deletion) compensated for the negative effects of STZ stress.
