Biogenesis of cytosolic ribosomes requires the essential iron–sulphur protein Rli1p and mitochondria

• DOI: 10.1038/sj.emboj.7600541
• Publication Date: 2005-01-20T14:23:50Z
• Authors: Gyula Kispal; Katalin Sipos; Heike Lange; Zsuzsanna Fekete; Tibor Bedekovics; Tamás Janáky; Jochen Bassler; Daili J Aguilar Netz; Janneke Balk; Carmen Rotte; Roland Lill
• Keywords: Iron-Sulfur Proteins; 570; 0303 health sciences; Saccharomyces cerevisiae Proteins; Base Sequence; Sequence Homology, Amino Acid; Genes, Fungal; Molecular Sequence Data; 610; Biological Transport, Active; Saccharomyces cerevisiae; Mitochondria; Protein Structure, Tertiary; 03 medical and health sciences; Cytosol; Peptide Initiation Factors; Protein Biosynthesis; Mutagenesis, Site-Directed; ATP-Binding Cassette Transporters; Amino Acid Sequence; DNA, Fungal; Ribosomes

Mitochondria perform a central function in the biogenesis of cellular iron-sulphur (Fe/S) proteins. It is unknown to date why this biosynthetic pathway is indispensable for life, the more so as no essential mitochondrial Fe/S proteins are known. Here, we show that the soluble ATP-binding cassette (ABC) protein Rli1p carries N-terminal Fe/S clusters that require the mitochondrial and cytosolic Fe/S protein biogenesis machineries for assembly. Mutations in critical cysteine residues of Rli1p abolish association with Fe/S clusters and lead to loss of cell viability. Hence, the essential character of Fe/S clusters in Rli1p explains the indispensable character of mitochondria in eukaryotes. We further report that Rli1p is associated with ribosomes and with Hcr1p, a protein involved in rRNA processing and translation initiation. Depletion of Rli1p causes a nuclear export defect of the small and large ribosomal subunits and subsequently a translational arrest. Thus, ribosome biogenesis and function are intimately linked to the crucial role of mitochondria in the maturation of the essential Fe/S protein Rli1p.