Mitochondrial viscosity, oxidative stress and autophagy responsive fluorescent Zn(II) complex for monitoring non-alcoholic fatty liver disease.

Accumulating evidence highlights the critical role of dysfunctional mitochondrial quality control in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). However, there is limited information available regarding of viscosity-related cellular metabolic processes of NAFLD. To address this, we developed a novel viscosity-sensitive fluorescent metal Zn(II) complex, LIFM-ZY-1, for monitoring viscosity changes with one-photon (OP) and two-photon (TP) fluorescence. It could effectively track cellular oxidative stress induced by lipotoxicity with viscosity changes, as reflected by viscosity changes in the OP/TP channel. Besides, LIFM-ZY-1 was capable of detecting non-selective mitophagy triggered by starvation in real time and selective mitophagy induced by autophagy drug rapamycin. Moreover, LIFM-ZY-1 successfully monitored the deterioration and therapeutic outcome of NAFLD mice with changing viscosity induced by overeating and autophagy drug empagliflozin. Overall, our findings demonstrated the potential of LIFM-ZY-1 as a valuable tool for real time monitoring NAFLD treatment through viscosity, oxidative stress and autophagy changes, offering valuable insights into the underlying biological processes and potential therapeutic strategies for NAFLD.