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Content archived on 2024-05-29

Investigating the function of the microsporidian mitosome using genomics and molecular cell biology

Final Activity Report Summary - MICRO ISC (Investigating the function of the microsporidian mitosome using genomics and molecular cell biology)

Microsporidia are highly specialised obligate intracellular parasites of eukaryotes, including humans, which demonstrate extreme reduction at the molecular, cellular and biochemical level. Even though they were long thought to be early branching eukaryotes lacking mitochondria, they were recently shown to contain a tiny mitochondrial remnant called a mitosome.

The function of the mitosome is unknown since microsporidians lack the genes for canonical mitochondrial functions, such as aerobic respiration and heme biosynthesis. The microsporidial genomes encode, however, several components of the mitochondrial iron-sulphur (Fe/S) cluster assembly machinery.

During my project I provided the first experimental insights into the metabolic function and localisation of these proteins. I cloned, functionally characterised and localised several central mitochondrial Fe/S cluster assembly components for the microsporidians encephalitozoon cuniculi and trachipleistophora hominis. Several microsporidial proteins could functionally replace their yeast counterparts in Fe/S protein biogenesis. In e. cuniculi, the iron (frataxin) and sulphur, i.e. cysteine desulphurase and Nfs1, donors and the scaffold protein (Isu1) co-located with mitochondrial Hsp70 to the mitosome, with the latter being consistent with the functional site for Fe/S cluster biosynthesis.

In t. hominis, mitochondrial Hsp70 and the essential sulphur donor (Nfs1) were still in the mitosome, even though, surprisingly, the main pools of Isu1 and frataxin were cytosolic, creating a conundrum of how these key components of Fe/S cluster biosynthesis coordinated their function. The observation that mitosomes of both species contained critical elements of a Fe/S cluster assembly machinery, which was essential in model eukaryotes for cell survival, strongly argued that this biosynthetic process was a key function of the microsporidian organelle.