Mechanisms of Mitochondrial Iron-Sulfur Protein Biogenesis.
Mitochondria are essential in most eukaryotes and are involved in numerous biological functions including ATP production, cofactor biosyntheses, apoptosis, lipid synthesis, and steroid metabolism. Work over the past two decades has uncovered the biogenesis of cellular iron-sulfur (Fe/S) proteins as the essential and minimal function of mitochondria. This process is catalyzed by the bacteria-derived iron-sulfur cluster assembly (ISC) machinery and has been dissected into three major steps: de novo synthesis of a [2Fe-2S] cluster on a scaffold protein; Hsp70 chaperone-mediated trafficking of the cluster and insertion into [2Fe-2S] target apoproteins; and catalytic conversion of the [2Fe-2S] into a [4Fe-4S] cluster and subsequent insertion into recipient apoproteins. ISC components of the first two steps are also required for biogenesis of numerous essential cytosolic and nuclear Fe/S proteins, explaining the essentiality of mitochondria. This review summarizes the molecular mechanisms underlying the ISC protein-mediated maturation of mitochondrial Fe/S proteins and the importance for human disease.
['Lill|Roland|R|', 'Freibert|Sven-A|SA|']
D018528:ATP-Binding Cassette Transporters D013437:Carbon-Sulfur Lyases D005288:Ferredoxins D005621:Friedreich Ataxia D005786:Gene Expression Regulation D054477:Glutaredoxins D006801:Humans D033862:Iron-Binding Proteins D007506:Iron-Sulfur Proteins D008928:Mitochondria D028361:Mitochondrial Diseases D024101:Mitochondrial Proteins D008958:Models, Molecular D018832:Molecular Chaperones D014176:Protein Biosynthesis D054730:Protein Interaction Domains and Motifs D017433:Protein Structure, Secondary D012441:Saccharomyces cerevisiae
ABC protein CIA machinery FRDA Fe/S cluster Fe/S disease Friedrich's ataxia ISC machinery MMDS cysteine desulfurase cytosolic iron-sulfur protein assembly machinery ferredoxin frataxin glutaredoxin iron-sulfur cluster assembly machinery multiple mitochondrial dysfunction syndromes