Lack of mitochondrial DNA impairs chemical hypoxia-induced autophagy in liver tumor cells through ROS-AMPK-ULK1 signaling dysregulation independently of HIF-1α
Hypoxia mimetic agents increase transcriptionally active HIF-1α in mtDNA-depleted cells. MtDNA depletion impairs chemical hypoxia-induced autophagy by dysregulating AMPK. AMPK activation by chemical hypoxia-induced ROS is blocked in cells lacking mtDNA. CoCl2 and DFO-induced autophagy is involved in cell survival and death, respectively. MtDNA-deficient cells are resistant to CoCl2-induced endoplasmic reticulum stress.