Evolutionary conservation and in vitro reconstitution of microsporidian iron–sulfur cluster biosynthesis

• Published in: Nature communications Vol. 8; no. 1; p. 13932
• Main Authors: Freibert, Sven-A., Goldberg, Alina V., Hacker, Christian, Molik, Sabine, Dean, Paul, Williams, Tom A., Nakjang, Sirintra, Long, Shaojun, Sendra, Kacper, Bill, Eckhard, Heinz, Eva, Hirt, Robert P., Lucocq, John M, Embley, T. Martin, Lill, Roland
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 04.01.2017; Nature Publishing Group; Nature Portfolio
• Subjects: 14; 14/28; 14/63; 631/181/757; 631/45/173; 631/80/642; 82; 82/83; Biological Evolution; Biosynthesis; Cell Nucleus - metabolism; Cytosol - metabolism; Fractionation; Fungal Proteins - biosynthesis; Fungal Proteins - genetics; Genomes; Humanities and Social Sciences; Iron; Iron-Sulfur Proteins - biosynthesis; Iron-Sulfur Proteins - genetics; Localization; Mitochondria; Mitochondria - metabolism; multidisciplinary; Pansporablastina - genetics; Pansporablastina - metabolism; Parasites; Phylogenetics; Phylogeny; Proteins; Science; Science (multidisciplinary); Sulfur; Yeast; United Kingdom > UK; Germany
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms13932

Microsporidians are obligate intracellular parasites that have minimized their genome content and sub-cellular structures by reductive evolution. Here, we demonstrate that cristae-deficient mitochondria (mitosomes) of Trachipleistophora hominis are the functional site of iron–sulfur cluster (ISC) assembly, which we suggest is the essential task of these organelles. Cell fractionation, fluorescence imaging and immunoelectron microscopy demonstrate that mitosomes contain a complete pathway for [2Fe–2S] cluster biosynthesis that we biochemically reconstituted using purified mitosomal ISC proteins. The T. hominis cytosolic iron–sulfur protein assembly (CIA) pathway includes the essential Cfd1–Nbp35 scaffold complex that assembles a [4Fe–4S] cluster as shown by spectroscopic methods in vitro . Phylogenetic analyses reveal that the ISC and CIA pathways are predominantly bacterial, but their cytosolic and nuclear target Fe/S proteins are mainly archaeal. This mixed evolutionary history of Fe/S-related proteins and pathways, and their strong conservation among highly reduced parasites, provides compelling evidence for the ancient chimeric ancestry of eukaryotes. The functions of the highly reduced mitochondria (mitosomes) of microsporidians are not well-characterized. Here, the authors show that the Trachipleistophora hominis mitosome is the site of iron–sulfur cluster assembly and that its retention is likely linked to its role in cytosolic and nuclear iron–sulfur protein maturation.