Gold nanoparticles induce autophagosome accumulation through size-dependent nanoparticle uptake and lysosome impairment

Xiaowei Ma, Yanyang Wu, Shubin Jin, Yuan Tian, Xiaoning Zhang, Yuliang Zhao, Li Yu, Xing Jie Liang

Research output: Contribution to journalArticle

377 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)8629-8639
Number of pages11
JournalACS Nano
Volume5
Issue number11
DOIs
StatePublished - Nov 22 2011

Keywords

  • autophagic flux
  • autophagosome accumulation
  • gold nanoparticles (AuNPs)
  • lysosomal pH
  • lysosome impairment

ASJC Scopus subject areas

  • Engineering(all)
  • Materials Science(all)
  • Physics and Astronomy(all)

Fingerprint Dive into the research topics of 'Gold nanoparticles induce autophagosome accumulation through size-dependent nanoparticle uptake and lysosome impairment'. Together they form a unique fingerprint.

Cite this