Abstract Silicon dioxide (SiO 2 ) is widely used as an anti-caking agent in food and cosmetics. PANoptosis is a highly complex inflammatory programmed death pathway and plays a crucial role in disease and toxic injury. This study investigated the damage caused by 50 nm, 300 nm, and 1 μm SiO 2 particles to the mice's colon and compared the toxicity differences among these particle sizes. The results showed that SiO 2 exposure induced ciliary damage and reduced intracellular serine content by inhibiting spermidine/spermine N1-acetyltransferase 1/2 (SAT1/2), thereby affecting mitochondrial one-carbon metabolism. Meanwhile, downregulation of mitochondrial overlapping with the m-complex activity 1 (OMA1)/optic atrophy 1 (OPA1) led to mitochondrial damage and mitochondrial reactive oxygen species (mtROS) release, eventually activating RIPK1-PANoptosome-mediated PANoptosis. Among them, 300 nm had the strongest effect on mitochondrial damage, 50 nm on apoptosis, and 1 μm on amino acid metabolism, one-carbon metabolism, necroptosis, and pyroptosis. In conclusion, SiO 2 exposure induced RIPK-mediated PANoptosis via the serine/mitochondrial/mtROS pathway. Graphical Abstract
Shi et al. (Thu,) studied this question.