The cytochrome oxidase defect in ISC-depleted yeast is caused by impaired iron-sulfur cluster maturation of the mitoribosome assembly factor Rsm22.

ABSTRACT: Mitochondria contain the bacteria-inherited iron-sulfur cluster assembly (ISC) machinery to generate cellular iron-sulfur (Fe/S) proteins. Mutations in human ISC genes cause severe disorders with a broad clinical spectrum and are associated with strong defects in mitochondrial Fe/S proteins, including respiratory complexes I-III. For unknown reasons, complex IV (aka cytochrome c oxidase), a non-Fe/S, heme-containing enzyme, is severely affected. Using yeast as a model, we show that depletion of Rsm22, the counterpart of the human mitoribosome assembly factor METTL17, phenocopies the defects observed upon impairing late-acting ISC proteins, that is, diminished activities of mitoribosomal translation and respiratory complexes III and IV. Rsm22 binds Fe/S clusters in vivo, thereby satisfactor

SUBMITTER: Muhlenhoff U 

PROVIDER: S-EPMC12375894 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature