Key Role of Microtubule and Its Acetylation in a Zinc Oxide Nanoparticle-Mediated Lysosome-Autophagy System.

ABSTRACT

Autophagy is a biological process that has attracted considerable attention as a target for novel therapeutics. Recently, nanomaterials (NMs) have been reported to modulate autophagy, which makes them potential agents for the treatment of autophagy-related diseases. In this study, zinc oxide nanoparticles (ZNPs) are utilized to evaluate NM-induced autophagy and debate the mechanisms involved. It is found that ZNPs undergo pH-dependent ion shedding and that intracellular zinc ions (Zn2+ ) play a crucial role in autophagy. Autophagy is activated with ZNPs treatment, which is inhibited after Zn2+ sequestration via ethylenediamine tetra-acetic acid. Lysosome-based autophagic degradation is halted after ZNPs treatment for more than 3 h and is accompanied by blockage of lysophagy, which renews impaired lysosomes. Furthermore, the microtubule (MT) system participates in ZNP-induced lysosome-autophagy system changes, especially in the fusion between autophagosomes and lysosomes. MT acetylation is helpful for protecting from ZNP-induced MT disruption, and it promotes the autophagic degradation process. In conclusion, this study provides valuable information on NM-induced lysosome-autophagy system changes, particularly with respect to the role of lysophagy and the MT system, which point to some attractive targets for the design of engineered nanoparticles.