Fig. 6
Cancer cells surviving chemotherapy increase OMA1 activity and decrease mitochondrial fusion and function to persist under oxidative stress. Cancer cells that survive chemotherapy enter a resistant cell state that increases their cell size and remain non-proliferative. Cells in this state have increased levels of reactive oxygen species (ROS) and exhibit fragmented mitochondria. Cells in this state increase OMA1 activity, cleaving L-OPA1 to S-OPA1, ultimately disrupting the mitochondrial cristae structure and reducing mitochondrial fusion. This altered cristae structure generates a diffuse proton gradient and decreases mitochondrial membrane potential, which lowers oxidative capacity as a survival mechanism against oxidative stress in these cells. This proposed mechanism requires further validation with rescue experiments in future studies. Created in BioRender. Li, M. (2025) https://BioRender.com/41jh49x.
