The Emerging Roles of Hydrogen Sulfide in Ferroptosis

Area of Science:

• Biochemistry
• Cell Biology
• Pathophysiology

Background:

• Ferroptosis, a lipid peroxidation-driven cell death, is implicated in diverse diseases like neurodegeneration and COPD.
• Hydrogen sulfide (H2S), a gasotransmitter, has emerged as a critical regulator of ferroptosis.
• Understanding H2S's role offers new therapeutic avenues for ferroptosis-related pathologies.

Purpose of the Study:

• To review the multifaceted role of H2S in ferroptosis.
• To highlight novel molecular targets and signaling pathways involved in H2S-mediated ferroptosis regulation.
• To discuss the therapeutic potential and challenges of H2S modulation in disease.

Main Methods:

• Literature review of ferroptosis and H2S research.
• Analysis of signaling pathways (e.g., p53, NO/Nrf2) and molecular targets (e.g., TfR1, xCT).
• Examination of preclinical and clinical data on H2S donors.

Main Results:

• H2S influences ferroptosis through various metabolic and signaling pathways.
• Inhibition of ferroptosis by H2S shows therapeutic promise in diseases like emphysema and TBI.
• Novel H2S donors are in early clinical trials, demonstrating safety and efficacy.

Conclusions:

• H2S is a crucial modulator of ferroptosis with significant therapeutic implications.
• Targeted delivery of H2S remains a key challenge for clinical translation.
• Further research into stable H2S donors and delivery systems is essential for advancing clinical trials.