Trehalose, sucrose and raffinose are novel activators of autophagy in human keratinocytes through an mTOR-independent pathway

Abstract

Trehalose is a natural disaccharide that is found in a diverse range of organisms but not in mammals. Autophagy is a process which mediates the sequestration, lysosomal delivery and degradation of proteins and organelles. Studies have shown that trehalose exerts beneficial effects through inducing autophagy in mammalian cells. However, whether trehalose or other saccharides can activate autophagy in keratinocytes is unknown. Here, we found that trehalose treatment increased the LC3-I to LC3-II conversion, acridine orange-stained vacuoles and GFP-LC3B (LC3B protein tagged with green fluorescent protein) puncta in the HaCaT human keratinocyte cell line, indicating autophagy induction. Trehalose-induced autophagy was also observed in primary keratinocytes and the A431 epidermal cancer cell line. mTOR signalling was not affected by trehalose treatment, suggesting that trehalose induced autophagy through an mTOR-independent pathway. mTOR-independent autophagy induction was also observed in HaCaT and HeLa cells treated with sucrose or raffinose but not in glucose, maltose or sorbitol treated HaCaT cells, indicating that autophagy induction was not a general property of saccharides. Finally, although trehalose treatment had an inhibitory effect on cell proliferation, it had a cytoprotective effect on cells exposed to UVB radiation. Our study provides new insight into the saccharide-mediated regulation of autophagy in keratinocytes.

SLC2A8 (GLUT8) is a mammalian trehalose transporter required for trehalose-induced autophagy

“…5 and ref. 19), yet mTORC inhibition was insufficient to induce autophagic flux in HepG2 hepatocytes and in primary hepatocytes in concordance with prior reports34675051. Trehalose-induced autophagy may be cell-type specific with respect to mTORC1 blockade.…”

The Effect of Silica Nanoparticles on Human Corneal Epithelial Cells

“…However, recently, several reports indicated that mTOR pathway is not the only control mechanism of autophagy. Autophagy can be regulated by various pathways which are independent of mTOR, and this suggests that these two pathways (mTOR and autophagy) are not always coupled to each other46474849. The uncoupling of mTOR and autophagy was observed in our study.…”

The Roles of Autophagy and the Inflammasome during Environmental Stress-Triggered Skin Inflammation

“…Autophagy induced by resveratrol could reduce UVB-induced apoptosis in keratinocytes, thus reducing malignant transformation [94]. Other natural components such as disaccharide trehalose and apigenin are also reported that can induce autophagy to against UVB-induced cell death [95,96]. In addition, a natural cyclopeptide, roseotoxin B, has also been demonstrated to trigger autophagy to overcome picryl chlororide-induced contact hypersensitivity in mice [97].…”