Mutations in mitochondrial ferredoxin FDX2 suppress frataxin deficiency.

ABSTRACT: Frataxin is a key component of an ancient, mitochondrial iron-sulfur cluster biosynthetic machinery, serving as an allosteric activator of the cysteine desulfurase NFS1 (refs. ^1-5). Loss of frataxin levels underlies Friedreich's ataxia⁶, the most common inherited ataxia. Yeast, Caenorhabditis elegans and human cells can tolerate loss of frataxin when grown in 'permissive' low oxygen tensions⁷. Here we conducted an unbiased, genome-scale forward genetic screen in C. elegans leveraging permissive and non-permissive oxygen tensions to discover suppressor mutations that bypass the need for frataxin. All mutations act dominantly and are in the ferredoxin FDX2/fdx-2 or in the cysteine desulfurase NFS1/nfs-1 genes, resulting in amino-acid substitutions at the FDX2

SUBMITTER: Meisel JD 

PROVIDER: S-EPMC12804076 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature