Mitochondrial ferritin attenuates cerebral ischaemia/reperfusion injury by inhibiting ferroptosis

Area of Science:

• Neuroscience
• Molecular Biology
• Pathology

Background:

• Ischaemic stroke is a leading cause of disability in aging populations.
• Iron accumulation exacerbates brain damage in cerebral ischaemia/reperfusion (I/R) injury.
• The role of mitochondrial ferritin (FtMt) in I/R injury is not well understood.

Purpose of the Study:

• To investigate the molecular function of mitochondrial ferritin (FtMt) in cerebral I/R injury.
• To determine if FtMt plays a protective role against I/R-induced brain damage and ferroptosis.

Main Methods:

• Examined FtMt levels in ischaemic mouse brains.
• Assessed brain damage and neurological deficits in wild-type and FtMt-deficient mice after I/R.
• Analyzed molecular markers of ferroptosis, inflammation, and iron metabolism.

Main Results:

• FtMt levels were upregulated in ischaemic brains.
• FtMt deficiency led to increased brain damage, neurological deficits, and ferroptosis markers (lipid peroxidation, disturbed glutathione).
• FtMt deficiency promoted inflammation and hepcidin-mediated ferroportin1 reduction, increasing iron levels and ferroptosis.

Conclusions:

• Mitochondrial ferritin (FtMt) plays a critical protective role against cerebral I/R-induced ferroptosis and brain damage.
• FtMt mitigates I/R injury by maintaining iron homeostasis and preventing ferroptosis.
• FtMt represents a potential therapeutic target for preventing or treating ischaemic stroke.