Rapamycin-regulated autophagy through mitochondrial function in lung carcinoma A549 cells

Lung cancer is the most leading cause of cancer-related death. Radio- and chemo- therapy resistance had associated with increased mitochondrial activity. The goal of this study was to investigate the role of mitochondrial DNA in human carcinoma A549 cells. Wild-type A549 and mitochondrial DNA-depleted A549 cells (A549 ρ 0 ) was used to study the role of mitochondria in rapamycin induced autophagy. Mitochondrial superoxide production were detected and measured by florescence microscopy. Western blot was used to detect autophagy and cell death to study the role of mitochondria in rapamycin induced autophagy. We observed depletion of mitochondrial DNA decrease proliferation and wound healing ability in A549 ρ 0 compared to wild-type A549 cells. Meanwhile, depletion of mtDNA raised inflammatory cytokine secretion in A549 ρ 0 cells. Depletion of mtDNA reduced rapamycin induced autophagy in A549 cells. The rapamycin induced cell death in A549 ρ 0 cells instead of autophagy in A549 cells. In conclusion, mitochondrial defects lead to increased lung inflammatory responses, reduced epithelial repair ability in A549 cells. These results revealed that A549 ρ 0 cells are more resistant to rapamycin induced autophagy than wild-type A549 cells. Finally, rapamycin likely in part induced cell death in A549 ρ 0 cells due to the depletion of mtDNA.