1,3-Dichloro-2-propanol\nInduced Renal Cell Ferroptosis\nvia the Circadian Clock Protein BMAL1 Targeting GPX4

1,3-Dichloro-2-propanol (1,3-DCP), a representative chloropropyl\nalcohol contaminant in food, has shown toxic effects on the kidney.\nFerroptosis is a newly identified cell death driven by iron-dependent\nlipid peroxidation that is associated with renal injury. However,\nthe role of 1,3-DCP in ferroptosis in renal cells remains unclear.\nIn this study, we found that ferroptosis was involved in a 1,3-DCP-induced\nrenal injury. Mechanistically, we revealed that 1,3-DCP triggered\nferroptosis by inhibiting GPX4 activity and disturbing iron homeostasis\nin NRK-52E cells. The circadian clock is crucial in modulating physiological\ncellular functions through the regulation of various downstream proteins.\nFurthermore, our findings also showed that 1,3-DCP triggered ferroptosis\nthrough interference with the circadian clock. The data showed that\nthe expression of GPX4 was regulated by clock core protein BMAL1.\n1,3-DCP interfered with GPX4 rhythmic expression through disordering\nBMAL1 and led to lipid peroxidation, ultimately inducing ferroptosis.\nIn conclusion, our study uncovered that BMAL1 was responsible for\ncontrolling GPX4 to mediate 1,3-DCP-induced ferroptosis. The BMAL1/GPX4\naxis may be a potentially novel pathway for ferroptosis. Our work\nmay offer a fresh perspective for toxicological research examining\nthe interactions between food pollutants, circadian clock, and ferroptosis.