Nutrient deficiency, excitotoxic injury, and oxidative stress caused by cerebral ischemia/reperfusion injury are important inducing factors of mitophagy and ferroptosis in neurons. Ferroptosis is an iron-dependent mode of cell death usually accompanied by a large accumulation of iron ions and lipid peroxides. Mitophagy is one of the forms of selective autophagy, which can maintain mitochondrial and cellular homeostasis by eliminating dysfunctional mitochondria. Mitophagy and ferroptosis are closely related to the pathological mechanism of ischemia/reperfusion injury. However, the function and mechanism of mitophagy in regulating ferroptosis are only beginning to be understood, and the relationship between mitophagy and ferroptosis after cerebral ischemia/reperfusion has not been elucidated. This article reviews the mechanism pathways of mitophagy and ferroptosis after cerebral ischemia/reperfusion, especially discusses the common regulatory factors of mitophagy and ferroptosis in cerebral reperfusion injury, and focuses on the therapeutic potential of mitophagy in regulating ferroptosis, in order to provide ideas for targeted treatment of cerebral ischemia/reperfusion injury.

Ferroptosis is a new non-apoptotic form of regulatory cell death, which is characterized by intracellular iron overload and excessive accumulation of lipid peroxides and reactive oxygen species (ROS). Ferroptosis is closely related to intracellular iron, amino acid, and lipid metabolism disorders. Ferroptosis is increasingly recognized as an important process mediating the pathogenesis and progression of acute ischemic stroke, and it can be involved in influencing acute ischemic stroke and acute ischemic stroke risk factors atherosclerosis, atrial fibrillation, hypertension, diabetes mellitus, and obstructive sleep apnea. Therefore, understanding the mechanisms of ferroptosis regulation in different diseases may have significant implications for the preventive treatment and improvement of prognosis in patients with acute ischemic stroke and patients with risk factors for acute ischemic stroke. This article reviews not only the specific important mechanisms of ferroptosis in the development of acute ischemic stroke, but also the relevant associations between risk factors for acute ischemic stroke and ferroptosis, and describes the current limitations and future directions of ferroptosis in the pathogenesis of acute ischemic stroke and its risk factors.