title: Evidence that the Entamoeba histolytica Mitochondrial Carrier Family Links Mitosomal and Cytosolic Pathways through Exchange of 3'-Phosphoadenosine 5'-Phosphosulfate and ATP.
abstract: Entamoeba histolytica, a microaerophilic protozoan parasite, possesses mitosomes. Mitosomes are mitochondrion-related organelles that have largely lost typical mitochondrial functions, such as those involved in the tricarboxylic acid cycle and oxidative phosphorylation. The biological roles of Entamoeba mitosomes have been a long-standing enigma. We previously demonstrated that sulfate activation, which is not generally compartmentalized to mitochondria, is a major function of E. histolytica mitosomes. Sulfate activation cooperates with cytosolic enzymes, i.e., sulfotransferases (SULTs), for the synthesis of sulfolipids, one of which is cholesteryl sulfate. Notably, cholesteryl sulfate plays an important role in encystation, an essential process in the Entamoeba life cycle. These findings identified a biological role for Entamoeba mitosomes; however, they simultaneously raised a new issue concerning how the reactions of the pathway, separated by the mitosomal membranes, cooperate. Here, we demonstrated that the E. histolytica mitochondrial carrier family (EhMCF) has the capacity to exchange 3'-phosphoadenosine 5'-phosphosulfate (PAPS) with ATP. We also confirmed the cytosolic localization of all the E. histolytica SULTs, suggesting that in Entamoeba, PAPS, which is produced through mitosomal sulfate activation, is translocated to the cytosol and becomes a substrate for SULTs. In contrast, ATP, which is produced through cytosolic pathways, is translocated into the mitosomes and is a necessary substrate for sulfate activation. Taking our findings collectively, we suggest that EhMCF functions as a PAPS/ATP antiporter and plays a crucial role in linking the mitosomal sulfate activation pathway to cytosolic SULTs for the production of sulfolipids.
authors.affiliation: Division of Molecular and Cellular Immunoscience, Department of Biomolecular Sciences, Faculty of Medicine, Saga University, Saga, Japan.
authors.forename: Fumika
authors.initials: F
authors.lastname: Mi-ichi
authors.affiliation: Proteo-Science Center, Ehime University, Matsuyama, Ehime, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Nozawa
authors.affiliation: Division of Molecular and Cellular Immunoscience, Department of Biomolecular Sciences, Faculty of Medicine, Saga University, Saga, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yoshida
authors.affiliation: Graduate School of Science and Engineering, Saitama University, Saitama, Japan tozawa@mail.saitama-u.ac.jp nozaki@nih.go.jp.
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Tozawa
authors.affiliation: Department of Parasitology, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo, Japan Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan tozawa@mail.saitama-u.ac.jp nozaki@nih.go.jp.
authors.forename: Tomoyoshi
authors.initials: T
authors.lastname: Nozaki
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D004748:Entamoeba histolytica / Q000235:genetics / Q000378:metabolism*; D008055:Lipids / Q000096:biosynthesis; D008928:Mitochondria / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D010724:Phosphoadenosine Phosphosulfate / Q000378:metabolism*; D021381:Protein Transport; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism*
chemical_list: D008055:Lipids; D033681:Mitochondrial Membrane Transport Proteins; D015800:Protozoan Proteins; C015518:sulfolipids; D010724:Phosphoadenosine Phosphosulfate; D000255:Adenosine Triphosphate; C022321:PAPS sulfotransferase; D015238:Sulfotransferases