Micro- and Nanosized Substances Cause Different Autophagy-Related Responses

Abstract

With rapid industrialization, humans produce an increasing number of products. The composition of these products is usually decomposed. However, some substances are not easily broken down and gradually become environmental pollutants. In addition, these substances may cause bioaccumulation, since the substances can be fragmented into micro- and nanoparticles. These particles or their interactions with other toxic matter circulate in humans via the food chain or air. Whether these micro- and nanoparticles interfere with extracellular vesicles (EVs) due to their similar sizes is unclear. Micro- and nanoparticles (MSs and NSs) induce several cell responses and are engulfed by cells depending on their size, for example, particulate matter with a diameter ≤2.5 μm (PM2.5). Autophagy is a mechanism by which pathogens are destroyed in cells. Some artificial materials are not easily decomposed in organisms. How do these cells or tissues respond? In addition, autophagy operates through two pathways (increasing cell death or cell survival) in tumorigenesis. Many MSs and NSs have been found that induce autophagy in various cells and tissues. As a result, this review focuses on how these particles interfere with cells and tissues. Here, we review MSs, NSs, and PM2.5, which result in different autophagy-related responses in various tissues or cells.

Keywords: autophagy; extracellular vesicles; microparticles; nanoparticles.

Figure 1

Schematic picture of several major endocytosis pathways for micro- and nanosized substances (MSs and NSs). MSs and NSs employ one or multiple endocytosis pathways to enter cells. The main endocytosis pathways of MSs or NSs include clathrin-mediated endocytosis, caveolae/lipid raft-mediated endocytosis, clathrin- and caveolin-independent endocytosis, macropinocytosis and phagocytosis. The possible mechanisms by which MSs and NSs modulate several cell responses, such as ER-stress, mitochondrial damage, lysosome dysfunction, ROS production, and autophagy, are summarized. MSs: Micro-sized substances; NSs: Nanosized substances.

Figure 2

Schematic picture of the macroautophagy process. MNs and NSs, including protein aggregates, damaged organs, plastics particles, dust, and silica are shown. LC3-II, Beclin 1, and p62 conjugate enzymes generate the phagophore form and then the surrounding MNs and NSs during the elongation stage. At the end of the elongation stage, the membrane is sealed to form a double-membrane vesicle, called the autophagosome, which contains degraded cellular enzymes. The autophagosome fuses with a lysosome, forming an autolysosome in which lysosomal enzymes degrade the cargo and release the degraded products into the cytoplasm. Undecomposed MSs and NSs, such as dust and silica, have carcinogenic potential.

Figure 3

Schematic picture of undecomposed MSs and NSs causing diseases. MSs and NSs can cause obstruction, inflammation, and accumulation in organs. MSs and NSs, such as dust, silica, asbestos, plastics MSs, and PM2.5, have been found to be related to diseases in previous studies.