Comprehensive cognition of yak (<i>Bos grunniens</i>) <i>AIFM2</i> gene and its anti-ferroptosis role in bisphenol A-induced fetal fibroblast model

Apoptosis-inducing factor mitochondrion-associated 2 (<i>AIFM2</i>) has been identified as a gene with anti-ferroptosis properties. To explore whether <i>AIFM2</i> exerts anti-ferroptosis role in yaks (<i>Bos grunniens</i>), we cloned yak <i>AIFM2</i> gene and analyzed its biological characteristics. The coding region of <i>AIFM2</i> had 1122 bp and encoded 373 amino acids, which was conserved in mammals. Next, RT-qPCR results showed an extensive expression of <i>AIMF2</i> in yak tissues. Furthermore, we isolated yak skin fibroblasts (YSFs) and established a bisphenol A (BPA)-induced ferroptosis model to further investigate the role of <i>AIFM2</i>. BPA elevated oxidative stress (reactive oxygen species, ROS) and lipid peroxidation (malondialdehyde, MDA and BODIPY), and reduced cell viability and antioxidant capacity (glutathione, GSH), with the severity depending on the dosage. Of note, a supplement of Ferrostatin-1 (Fer), an inhibitor of ferroptosis, restored the previously mentioned indicators. Subsequently, we constructed an <i>AIFM2</i> overexpression vector and designed <i>AIFM2</i> specific interfering siRNAs, which were transfected into YSFs. The results showed that overexpressing <i>AIFM2</i> alleviated ferroptosis, characterizing by significant changes of cell viability, ROS, BODIPY, MDA and GSH. Meanwhile, interfering <i>AIFM2</i> aggravated ferroptosis, demonstrating the critical anti-ferroptosis role of the yak <i>AIFM2</i> gene. This study shed light on further exploring the molecular mechanism of <i>AIFM2</i> in plateau adaptability.