Journal Article Ppublish
PubMed: 40768618 DOI: 10.1002/1873-3468.70129
The cytochrome oxidase defect in ISC-depleted yeast is caused by impaired iron-sulfur cluster maturation of the mitoribosome assembly factor Rsm22.
FEBS Lett 599(16):2301-2317
Authors: Ulrich Mühlenhoff, Dominik Trauth, Weronika Śliwińska, Linda Boss, Roland Lill
Affiliations
- Institut für Zytobiologie im Zentrum SYNMIKRO, Philipps-Universität Marburg, Germany.
- Institut für Zytobiologie im Zentrum SYNMIKRO, Philipps-Universität Marburg, Germany. Department of Bioenergetics, Faculty of Biology, Institute of Molecular Biology and Biotechnology, Adam Mickiewicz University, Poznań, Poland.
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 satisfactorily explaining the defect of respiratory complex IV in ISC-deficient cells, because this complex contains three mitochondrial DNA-encoded subunits. Impact statement Defects in mitochondrial Fe/S protein biogenesis also impact respiratory complex IV (COX), even though it lacks Fe/S clusters. Here, we show that the mitoribosome assembly factor Rsm22 binds Fe/S clusters in vivo. Rsm22 maturation defects impair mitoribosomal protein translation including COX subunits, explaining the COX defects in Fe/S cluster-deficient cells.
MeSH
Cells, Genes, Mitochondrial Ribosomes, Yeasts, Biophysics, Biochemistry, Cytochromes, Mitochondria, Organelle Biogenesis, Electron Transport Complex Iv