Evolutionary conservation and in vitro reconstitution of microsporidian iron-sulfur cluster biosynthesis.
Sven-A FreibertAlina V GoldbergChristian HackerSabine MolikPaul DeanTom A WilliamsSirintra NakjangShaojun LongKacper SendraEckhard BillEva HeinzRobert P HirtJohn M LucocqT Martin EmbleyRoland LillPublished in: Nature communications (2017)
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.
Keyphrases
- fluorescence imaging
- genome wide
- cell therapy
- metal organic framework
- single cell
- high resolution
- iron deficiency
- photodynamic therapy
- aqueous solution
- reactive oxygen species
- cell death
- molecular docking
- dna methylation
- high throughput
- cell wall
- mesenchymal stem cells
- stem cells
- gene expression
- visible light
- small molecule
- single molecule
- amino acid
- high speed
- binding protein
- mass spectrometry
- endoplasmic reticulum
- drug induced