Sulfate Activation in Mitosomes Plays an Important Role in the Proliferation of Entamoeba histolytica

Abstract

Mitochondrion-related organelles, mitosomes and hydrogenosomes, are found in a phylogenetically broad range of organisms. Their components and functions are highly diverse. We have previously shown that mitosomes of the anaerobic/microaerophilic intestinal protozoan parasite Entamoeba histolytica have uniquely evolved and compartmentalized a sulfate activation pathway. Although this confined metabolic pathway is the major function in E. histolytica mitosomes, their physiological role remains unknown. In this study, we examined the phenotypes of the parasites in which genes involved in the mitosome functions were suppressed by gene silencing, and showed that sulfate activation in mitosomes is important for sulfolipid synthesis and cell proliferation. We also demonstrated that both Cpn60 and unusual mitochondrial ADP/ATP transporter (mitochondria carrier family, MCF) are important for the mitosome functions. Immunoelectron microscopy demonstrated that the enzymes involved in sulfate activation, Cpn60, and mitochondrial carrier family were differentially distributed within the electron dense, double membrane-bounded organelles. The importance and topology of the components in E. histolytica mitosomes reinforce the notion that they are not “rudimentary” or “residual” mitochondria, but represent a uniquely evolved crucial organelle in E. histolytica.

Author Summary

The mitochondrion and its related organelles are ubiquitous in all extant eukaryotic cells. The mitochondria are believed to have originated from the endosymbiosis of α-proteobacteria in an ancestral eukaryote, and show diverse structures, contents, and functions. Evolution and diversification of mitochondrion-related organelles remains one of the central themes in biology. Entamoeba histolytica, which causes intestinal and extraintestinal amebiasis in humans, possesses a highly divergent form of mitochondrion-related organelles, named “mitosomes.” Previously, we demonstrated that sulfate activation is the major function of mitosomes in E. histolytica. As the sulfate activation pathway was discovered only in the cytoplasm and plastids in other eukaryotic organisms, its compartmentalization to mitosomes is unprecedented. In this study, we showed that this pathway is important for sulfolipid synthesis and cell proliferation in E. histolytica. Together, we infer that E. histolytica mitosomes are not just rudimentary or residual mitochondria, but important for proliferation of E. histolytica. Thus, E. histolytica represents a useful model to understand evolutionary constraints of mitochondrion-related organelles in eukaryotes.