Vitamin B2 metabolism promotes FSP1 stability to prevent ferroptosis - PubMed
3 hours ago
- #FSP1
- #vitamin B2
- #ferroptosis
- Ferroptosis is a regulated form of cell death driven by excessive lipid peroxidation and is a promising therapeutic target in cancer.
- Ferroptosis suppressor protein 1 (FSP1) is a critical regulator of ferroptosis resistance, but its expression and stability mechanisms are not well understood.
- CRISPR-Cas9 screens identified riboflavin kinase and FAD synthase, enzymes essential for synthesizing FAD from vitamin B2, as key contributors to FSP1 stability.
- FAD binding is crucial for both FSP1 activity and stability; deficiency or mutations blocking FSP1-FAD binding trigger degradation via the ubiquitin-proteasome pathway involving E3 ligase RNF8.
- Vitamin B2 supports ferroptosis resistance through FAD cofactor binding, ensuring FSP1 stability and function, unlike other vitamins that scavenge radicals.
- This study highlights a novel link between vitamin B2 metabolism and ferroptosis resistance, with potential therapeutic implications for cancer targeting FSP1.