Hemocyanin modulates ferroptosis through a HSP90-dependent antioxidant function in shrimp

Area of Science:

• Aquatic biology
• Cellular biology
• Biochemistry

Background:

• Ferroptosis, an iron-dependent cell death, is vital for homeostasis and stress response in mammals and shrimp.
• The regulatory mechanisms of ferroptosis in marine animals, particularly shrimp, are not well understood.

Purpose of the Study:

• To investigate the role of hemocyanin in modulating ferroptosis in the shrimp Penaeus vannamei.
• To identify molecular interactions involved in ferroptosis regulation in shrimp.

Main Methods:

• Analysis of gene expression during ferroptosis in shrimp.
• Investigation of hemocyanin and heat shock protein 90 (HSP90) interactions.
• Assessment of cellular viability, ferrous iron levels, and lipid peroxidation.

Main Results:

• Hemocyanin, particularly its small subunit, significantly inhibits ferroptosis in shrimp hepatopancreas.
• Shrimp exhibit reduced GPX4 expression and hemocyanin depletion during ferroptosis.
• A novel interaction between hemocyanin and HSP90 was identified, which reduces reactive oxygen species (ROS).
• Depletion of hemocyanin or HSP90 leads to increased Fe2+, lipid peroxidation, and decreased cell viability.

Conclusions:

• Hemocyanin plays a central role in protecting shrimp against oxidative damage via ferroptosis modulation.
• The hemocyanin-HSP90 interaction is key to reducing ROS during ferroptosis.
• Hemocyanin presents a potential therapeutic target for improving aquaculture immunity and stress resilience.