The mitosome of the anaerobic parasitic protist Entamoeba histolytica: A peculiar and minimalist mitochondrion-related organelle

Abstract

The simplest class of mitochondrion-related organelles (MROs) is the mitosome, an organelle present in a few anaerobic protozoan parasites such as Entamoeba histolytica, Giardia intestinalis, and Cryptosporidium parvum. E. histolytica causes amoebiasis in humans, deemed as one of the important, yet neglected tropical infections in the world. Much of the enigma of the E. histolytica mitosome circles around the obvious lack of a majority of known mitochondrial components and functions exhibited in other organisms. The identification of enzymes responsible for sulfate activation (AS, IPP, and APSK) and a number of lineage-specific proteins such as the outer membrane beta-barrel protein (MBOMP30), and transmembrane domain-containing proteins that bind to various organellar proteins (ETMP1, ETMP30, EHI_170120, and EHI_099350) showcased the remarkable divergence of this organelle compared to the other MROs of anaerobic protozoa. Here, we summarize the findings regarding the biology of the mitosomes in E. histolytica, from their discovery up to the present understanding of its roles and interactions. We also include current advances and future perspectives on the biology, biochemistry, and evolution of the mitosomes of E. histolytica.

Keywords: Entamoeba histolytica; membrane contact site; mitochondrion-related organelle; mitosome; mitosome fission; protein import; sulfate activation.

FIGURE 1

Mechanisms and components are currently known in the mitosome of Entamoeba histolytica. Protein import begins with the binding of mitosome‐targeted proteins to the cytosolic receptor of the translocase of the outer membrane (Tom), Tom60, which docks to the Tom40 channel. Proteins pass through Tom40, to the intermembrane space where unknown proteins sort them for assembly to the outer membrane via Sam50 (for beta‐barrel proteins) or transmit them to the also unidentified translocase of the inner membrane for delivery to the matrix. Soluble proteins are folded via heat‐shock protein (mtHsp70) and chaperonins (Cpn60 and Cpn10) in the matrix. Metabolite transport in the outer membrane likely occurs through the novel beta‐barrel protein MBOMP30, or the Tom40. Three inner membrane channels are identified, namely the sodium sulfate transporter (NaS), phosphate carrier (PiC), and ATP‐ADP carrier (AAC). In the matrix, three enzymes perform activation of sulfate by three enzyme‐catalyzed reactions. ATP sulfurylase (AS) catalyzes the formation of adenosine‐5′‐phosphosulfate (APS) using ATP and inorganic sulfate. Inorganic pyrophosphatase (IPP) degrades pyrophosphates into phosphates. APS kinase (APSK) phosphorylates APS to form 3′‐phosphoadenosine‐5′‐phosphosulfate (PAPS). The product PAPS is exported to the cytosol, reacts with cholesterol via sulfotransferase 6 (SULT6) to produce cholesteryl sulfate, which is secreted outside the cell, and is known to induce trophozoite to cyst formation (encystation). Other secreted sulfolipids (SL‐II, SL‐III, SL‐IV, and SL‐V) synthesized in the cytosol by SULT1‐5 and SULT7‐9, were demonstrated to be essential to trophozoite proliferation. Mitosome fission occurs via the heterooligomer complex of DrpA and DrpB. The binding of the cytosolic Drps to the outer membrane of mitosomes is still unclear as the Drp receptor is not yet identified. Several Entamoeba‐specific transmembrane domain‐containing proteins (ETMP1, ETMP30, EHI_099350, and EHI_170120) are likely involved in establishing membrane contact sites with other organelles specifically endosomes, the Golgi apparatus, ER, and peroxisomes, respectively. Created with BioRender.com