Silica sub-microspheres induce autophagy in an endocytosis dependent manner

The health risk of exposure to manufactured nano- and submicro-materials leads to an increasing effort to explore their biological effects and potential toxicity in detail. Here, we show that silica sub-microspheres (0.1 to 2.1 μm in diameter), the major component of dust or particulate matter less than 2.5 μm (PM 2.5), induce autophagy depending on the levels of cellular endocytosis. Due to the suitable size for cellular endocytosis, 0.5–0.7 μm silica particles induce the highest levels of autophagy among particles from 0.1 to 2.1 μm in diameter. Changes in cellular endocytosis of silica sub-microspheres lead to alteration of autophagy levels. Furthermore, dephosphorylation of FOXO3A and subsequent translocation to the nucleus may be associated with this autophagy process. Our results reveal the manner in which silica sub-microspheres induce autophagy, emphasize the potential risk of endocytosis of fine particles or other non-degradable materials, and suggest a new signaling pathway involved with autophagy induced by sub-micromaterials.