Cerium oxide nanoparticles (nanoceria) are widely used in a variety of 
industrial applications including UV filters and catalysts. The expanding 
commercial scale production and use of ceria nanoparticles have inevitably 
increased the risk of release of nanoceria into the environment as well as the 
risk of human exposure. The use of nanoceria in biomedical applications is also 
being currently investigated because of its recently characterized antioxidative 
properties. In this study, we investigated the impact of ceria nanoparticles on 
the lysosome-autophagy system, the main catabolic pathway that is activated in 
mammalian cells upon internalization of exogenous material. We tested a battery 
of ceria nanoparticles functionalized with different types of biocompatible 
coatings (N-acetylglucosamine, polyethylene glycol and polyvinylpyrrolidone) 
expected to have minimal effect on lysosomal integrity and function. We found 
that ceria nanoparticles promote activation of the transcription factor EB, a 
master regulator of lysosomal function and autophagy, and induce upregulation of 
genes of the lysosome-autophagy system. We further show that the array of 
differently functionalized ceria nanoparticles tested in this study enhance 
autophagic clearance of proteolipid aggregates that accumulate as a result of 
inefficient function of the lysosome-autophagy system. This study provides a 
mechanistic understanding of the interaction of ceria nanoparticles with the 
lysosome-autophagy system and demonstrates that ceria nanoparticles are 
activators of autophagy and promote clearance of autophagic cargo. These results 
provide insights for the use of nanoceria in biomedical applications, including 
drug delivery. These findings will also inform the design of engineered 
nanoparticles with safe and precisely controlled impact on the environment and 
the design of nanotherapeutics for the treatment of diseases with defective 
autophagic function and accumulation of lysosomal storage material.