Photo-protective role of ATG5/ATG7-independent alternative autophagy in human keratinocytes

Excessive exposure to sunlight, especially to ultraviolet B (UVB), results in DNA damage and a cutaneous inflammatory reaction commonly known as sunburn, which increases skin cancer risks. UVB-induced inflammasome activation in epidermal keratinocytes mediates the cutaneous inflammatory response, but the intracellular machinery that maintains skin homeostasis by suppressing UVB-induced inflammasome activation is unclear. Here, we summarize our recent work on the protective role of alternative autophagy against UVB-induced NLRP3 (NLR family pyrin domain containing 3) inflammasome activation in human keratinocytes. We found that UVB radiation induces ATG5/ATG7-independent alternative (noncanonical) autophagy, which leads to suppression of NLRP3 inflammasome activation through the clearance of damaged mitochondria in UVB-irradiated keratinocytes. Our findings indicate that ATG5/ATG7-independent alternative autophagy, rather than conventional autophagy, may play a key role in mitigating inflammatory responses, and restoring skin homeostasis after UV radiation.