Redox Network Dysfunction: Integrating Ferroptosis and Cuproptosis Across Human Diseases

Area of Science:

• Biochemistry and Molecular Biology
• Cellular Biology
• Pathology

Background:

• Oxidative stress (OS) is a dynamic disturbance of cellular redox networks, not just an oxidant-antioxidant imbalance.
• Ferroptosis and cuproptosis are regulated, metal-dependent cell death pathways crucial in linking OS to disease.
• These cell death mechanisms are implicated in metabolic dysfunction, inflammation, and tissue injury across various pathologies.

Purpose of the Study:

• To review and integrate findings on ferroptosis and cuproptosis as unifying mechanisms in OS-related diseases.
• To explore the role of lipid peroxidation, glutathione-GPX4 activity, and metal ions in distinct redox signatures.
• To highlight shared redox pathways connecting metal-dependent cell death to systemic inflammation and immune dysregulation.

Main Methods:

• Integration of biochemical, lipidomic, and metallomic study findings.
• Examination of ferroptosis and cuproptosis in cutaneous, metabolic, cardiovascular, infectious, neurodegenerative, and oncologic conditions.
• Discussion of analytical tools like redox lipidomics, metallomic profiling, and AI-based classification.

Main Results:

• Ferroptosis and cuproptosis generate distinct redox signatures involving lipid peroxidation, GSH-GPX4 activity, and organelle communication.
• Shared redox pathways connect iron and copper-dependent cell death to systemic inflammation, immune dysregulation, and chronic tissue damage.
• Common oxidative markers (oxidized phospholipids, aldehydes, metal imbalance) indicate disease severity and potential therapeutic targets.

Conclusions:

• Ferroptosis and cuproptosis are unifying mechanisms connecting OS to multisystem diseases.
• Oxidative markers and metal-dependent cell death pathways offer opportunities for diagnostic refinement.
• Precision redox therapies targeting these pathways represent a promising future direction.