Mitochondrial ATP and labile fe (II) pool simultaneous imaging in ferroptosis regulated by energy-stress mediated AMPK activation

Ferroptosis was a kind of widely-concerned cell death pathway to overcome drug-resistance in tumor therapies. Mitochondria, as the center of iron utilization and cell homeostasis, was studied for many years in the field of ferroptosis. Mitochondrial iron homeostasis was closely twisted with ATP production and energy stress. So, we developed a case of fluorescent probe with dual-emission to reveal the connection between ATP and LIP (liable iron (II) pool). We showed the enhanced iron uptake by extracellular ATP and activation of mitochondrial ATP in iron abundant environment through confocal fluorescence imaging in vitro and in vivo. For further research, we found and visualized the facilitation of ferroptosis by ATP and Fe2+ in ferroptosis-inert cell lines by ATP-Fe. Through confocal imaging of ATP-Fe, we also observed the morphology of cells and the mitochondrial ATP and LIP in ferroptosis regulated by energy-stress mediated AMPK activation or inhibition. Our research hinted that ATP-Fe could be a powerful tool to indicated iron homeostasis, mitochondrial morphology and metabolism in resolving ferroptosis-resistance and drug-resistance.