Urechistachykinin I triggers mitochondrial dysfunction leading to a ferroptosis-like response in Saccharomyces cerevisiae.

Abstract

The purpose of this paper was to demonstrate the antimicrobial activity of urechistachykinin I (LRQSQFVGSR-NH2) extracted from Urechis unicinctus,and its mode of action dependent on mitochondrial dysfunction. The antifungal activity of urechistachykinin I generated reactive oxygen species (ROS), as demonstrated with MitoSOX Red and hydroxyphenyl fluorescein (HPF). Overaccumulation of ROS caused oxidative damage to cells by inducing mitochondrial dysfunction. Mitochondrial disruption resulted in cell death, creating several hallmarks that included lipid peroxidation, glutathione oxidation, and depolarization. Moreover, the loss of mitochondria changed the calcium ion imbalance by depolarization of the mitochondrial membrane. In particular, iron accumulation and DNA fragmentation measurement determined the type of cell death. Our results indicate that urechistachykinin I treatment induced ferroptosis-like death in Saccharomyces cerevisiae via mitochondrial dysfunction. Urechistachykinin I treatment induced mitochondrial dysfunction in S. cerevisiae by generating ROS, and the subsequent oxidative damage caused the ferroptosis-like cell death.