title: Gold nanoparticles induce autophagosome accumulation through size-dependent nanoparticle uptake and lysosome impairment.
abstract: Development of nanotechnology calls for a comprehensive understanding of the impact of nanomaterials on biological systems. Autophagy is a lysosome-based degradative pathway which plays an essential role in maintaining cellular homeostasis. Previous studies have shown that nanoparticles from various sources can induce autophagosome accumulation in treated cells. However, the underlying mechanism is still not clear. Gold nanoparticles (AuNPs) are one of the most widely used nanomaterials and have been reported to induce autophagosome accumulation. In this study, we found that AuNPs can be taken into cells through endocytosis in a size-dependent manner. The internalized AuNPs eventually accumulate in lysosomes and cause impairment of lysosome degradation capacity through alkalinization of lysosomal pH. Consistent with previous studies, we found that AuNP treatment can induce autophagosome accumulation and processing of LC3, an autophagosome marker protein. However, degradation of the autophagy substrate p62 is blocked in AuNP-treated cells, which indicates that autophagosome accumulation results from blockade of autophagy flux, rather than induction of autophagy. Our data clarify the mechanism by which AuNPs induce autophagosome accumulation and reveal the effect of AuNPs on lysosomes. This work is significant to nanoparticle research because it illustrates how nanoparticles can potentially interrupt the autophagic pathway and has important implications for biomedical applications of nanoparticles.
authors.affiliation: Laboratory of Nanomedicine and Nanosafety, Division of Nanomedicine and Nanobiology, National Center for Nanoscience and Technology, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Ma
authors.forename: Yanyang
authors.initials: Y
authors.lastname: Wu
authors.forename: Shubin
authors.initials: S
authors.lastname: Jin
authors.forename: Yuan
authors.initials: Y
authors.lastname: Tian
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Zhang
authors.forename: Yuliang
authors.initials: Y
authors.lastname: Zhao
authors.forename: Li
authors.initials: L
authors.lastname: Yu
authors.forename: Xing-Jie
authors.initials: XJ
authors.lastname: Liang
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D001692:Biological Transport; D002460:Cell Line; D006046:Gold / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D008247:Lysosomes / Q000187:drug effects*; D053768:Metal Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D051381:Rats; D014617:Vacuoles / Q000187:drug effects* / Q000378:metabolism
chemical_list: D006046:Gold