Monday, May 25, 2026

Targeting competitive Fe–S regulation to treat Friedreich’s ataxia

Campos J, Ferreira J. Targeting competitive Fe–S regulation to treat Friedreich’s ataxia. Trends in Pharmacological Sciences, 2026; 0 DOI: 10.1016/j.tips.2026.04.010

Recent discoveries reveal that frataxin (FXN) and ferredoxin 2 (FDX2) competitively regulate mitochondrial iron–sulfur (Fe–S) cluster biosynthesis through their binding to the cysteine desulfurase NFS1 and the iron-sulfur cluster scaffold protein ISCU2 complex. Here, we discuss the potential of rationally designed peptide inhibitors targeting the FDX2–NFS1 interaction as a strategy to mitigate FXN deficiency and restore Fe–S cluster biosynthesis.