Ferroptosis in plants: Regulatory mechanisms and potential applications from plant physiology to human diseases.

Ferroptosis is a novel form of regulated cell death characterized by iron-dependent lipid peroxidation, which is mediated by multi-pathway cascades involving dysregulated iron metabolism, polyunsaturated fatty acids (PUFAs) oxidation, and impaired antioxidant defense systems. This form of cell death is closely implicated in the pathophysiology of various human diseases, including cancer, neurological disorders, ischemia-reperfusion injury, renal damage, and hematological diseases. Recent studies have expanded the understanding of ferroptosis to plants, where it plays pivotal roles in responding to biotic/abiotic stresses, activating defense signaling networks, and maintaining metabolic homeostasis. These findings provide new insights into how plants adapt to adverse environments and resist pathogens. Furthermore, diverse bioactive compounds derived from plants can modulate core mechanisms of ferroptosis, demonstrating potential for antitumor therapy and other diseases. Furthermore, plant-derived bioactive compounds exhibit broad pharmacological properties and can modulate the core mechanisms of ferroptosis, thereby showing great potential in the treatment of ferroptosis-related diseases such as tumors, autoimmune disorders, and neurodegenerative diseases. This review comprehensively elaborates on the primary regulatory mechanisms of ferroptosis, systematically analyzes iron-dependent cell death in plants, and explores the crosstalk between plant ferroptosis and stress adaptation. It also focuses on the regulatory effects of plant bioactive compounds on ferroptosis and their therapeutic potential, aiming to provide innovative strategies for crop protection in agricultural production and novel approaches for combating human diseases associated with ferroptosis.