Defects in the Maturation of Mitochondrial Iron-Sulfur Proteins: Biophysical Investigation of the MMDS3 Causing Gly104Cys Variant of IBA57.

ABSTRACT: Multiple mitochondrial dysfunctions syndrome type 3 (MMDS3) is a rare autosomal recessive mitochondrial leukoencephalopathy caused by biallelic pathogenic variants in the IBA57 gene. The gene protein product, IBA57, has an unknown role in iron-sulfur (Fe-S) cluster biogenesis but is required for the maturation of mitochondrial [4Fe-4S] proteins. To better understand the role of IBA57 in MMDS3, we have investigated the impact of the pathogenic p.Gly104Cys (c.310G > T) variant on the structural and functional properties of IBA57. The Gly104Cys variant has been associated with a severe MMDS3 phenotype in both compound heterozygous and homozygous states, and defects in the activity of mitochondrial respiratory complexes and lipoic acid-dependent enzymes have been demonstrated in the aff

SUBMITTER: Bargagna B 

PROVIDER: S-EPMC11476781 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature