Lipid peroxidation intrinsically induces mitochondrial iron overload via Bach1-HO-1 signaling to promote cardiac ferroptosis

Background: Lipid peroxidation and iron accumulation are hallmarks of ferroptosis, a form of cell death characterized by iron-dependent oxidative damage to cellular membranes. However, the molecular link between lipid peroxidation and iron overload in the execution of ferroptosis remains elusive. Moreover, the pathophysiological implications of the interaction between lipid peroxidation and iron overload in cardiac homeostasis and remodeling are also unknown. Methods: We assessed the role of lipid peroxidation in mediating cardiac iron overload and ferroptosis using genetic mouse models. We also performed molecular and cellular biology studies to elucidate the mechanisms by which lipid peroxidation regulates iron homeostasis and ferroptosis signaling in cardiomyocytes. Results: deficiency. Conclusions: These findings identified a mechanistic link between lipid peroxidation and iron overload via the Bach1-HO-1 signaling pathway, revealing new regulators and molecular targets for cardiac ferroptosis.