Journal Article

Entamoeba mitosomes play an important role in encystation by association with cholesteryl sulfate synthesis

Ghulam Jeelani, Hiroki Yoshida, Shouko Takao, Tetsuo Hashimoto, Hiromitsu Hara, Fumika Mi-ichi, Tomoyoshi Nozaki, Tomofumi Miyamoto

2015

Overview

Significance Evolution and diversification of organelles is a central topic in biology. Mitochondrion-related organelles (MROs) are highly modified forms of mitochondria found in anaerobic eukaryotes. MROs show a spectrum of functions that are either reduced or modified from those of canonical mitochondria by environmental constraints and evolutionary selection. Hence, elucidation of MRO functions will improve our understanding of organelle evolution and the speciation of eukaryotes. Here, we substantiate a role of the Entamoeba mitosome, a type of MRO, by showing that cholesteryl sulfate synthesized through a mitosomal pathway regulates differentiation that is essential for the parasite’s life cycle. These findings support the contribution of an endosymbiont-derived organelle to parasitism, a previously unrecognized concept that casts new light on organelle evolution. Hydrogenosomes and mitosomes are mitochondrion-related organelles (MROs) that have highly reduced and divergent functions in anaerobic/microaerophilic eukaryotes. Entamoeba histolytica , a microaerophilic, parasitic amoebozoan species, which causes intestinal and extraintestinal amoebiasis in humans, possesses mitosomes, the existence and biological functions of which have been a longstanding enigma in the evolution of mitochondria. We previously demonstrated that sulfate activation, which is not generally compartmentalized to mitochondria, is a major function of E . histolytica mitosomes. However, because the final metabolites of sulfate activation remain unknown, the overall scheme of this metabolism and the role of mitosomes in Entamoeba have not been elucidated. In this study we purified and identified cholesteryl sulfate (CS) as a final metabolite of sulfate activation. We then identified the gene encoding the cholesteryl sulfotransferase responsible for synthesizing CS. Addition of CS to culture media increased the number of cysts, the dormant form that differentiates from proliferative trophozoites. Conversely, chlorate, a selective inhibitor of the first enzyme in the sulfate-activation pathway, inhibited cyst formation in a dose-dependent manner. These results indicate that CS plays an important role in differentiation, an essential process for the transmission of Entamoeba between hosts. Furthermore, we show that Mastigamoeba balamuthi , an anaerobic, free-living amoebozoan species, which is a close relative of E . histolytica , also has the sulfate-activation pathway in MROs but does not possess the capacity for CS production. Hence, we propose that a unique function of MROs in Entamoeba contributes to its adaptation to its parasitic life cycle.

• Publisher: National Academy of Sciences,National Acad Sciences
• Subject: Adaptation, Biological - physiology / Archamoebae - physiology / Biological Evolution / Biological Sciences / Biosynthetic Pathways - physiology / Chlorates - pharmacology / Cholesterol Esters - biosynthesis / Cholesterol Esters - isolation & purification / Computational Biology / Culture media / Disease transmission / Dose-Response Relationship, Drug / encystment / Entamoeba / Entamoeba - physiology / Entamoeba histolytica / Eukaryotes / eukaryotic cells / evolution / Fluorescent Antibody Technique, Indirect / Life cycles / Lipids / Magnetic Resonance Spectroscopy / Mass Spectrometry / Mastigamoeba balamuthi / Metabolites / Mitochondria / Mitochondria - metabolism / Mitochondria - physiology / parasites / parasitism / Phylogeny / PNAS Plus / Protozoa / Real-Time Polymerase Chain Reaction / Species Specificity / Sulfates / Sulfotransferases - genetics