Biology subjects

Boshoven, C.

Publications and source records attributed to Boshoven, C..

7 recordsLinked to original sources

bioRxiv2026

Unique mitochondrial carrier has a role in mitochondrial dynamics during Plasmodium falciparum host switching

Malaria-causing parasites from the Plasmodium genus possess a mitochondrion that is essential across all life-cycle stages and highly divergent from its hosts, making it a suitable drug target. Transport of metabolites across the inner membrane of this metabolically active organelle is mediated by mitochondrial carrier (MC) proteins. Among these, the apicomplexan-specific MC1 (AMC1) stands out due to its likely essential function and limited conservation even within the Apicomplexa phylum. Bioinformatics and structural predictions reveal that P. falciparum AMC1 (PfAMC1) lacks canonical gating residues and shows a distorted membrane barrel, suggesting it may not function as a transporter. Using two independent mutant parasite lines, we demonstrate that PfAMC1 localises to the periphery of mitochondria, which exhibit increased dispersion and rounding during male gametogenesis, when the C-terminus is modified. Additionally, we identify the mammalian MTCH2, the function of which is still debated, as a potential structural homologue of PfAMC1, opening new avenues for research. Our findings emphasize the unique role of PfAMC1 in mitochondrial dynamics and lay the groundwork for further exploration of its molecular mechanism.

microbiology↗

bioRxiv2026

Plasmodium falciparum stomatin-like protein forms a putative complex with a metalloprotease in distinct mitochondrial loci

Withdrawal statementThis manuscript has been withdrawn owing to a duplicate posting of manuscript number BIORXIV/2024/604071. This was a technical error for which the authors are not responsible, and this DOI for the work should not be cited as reference. The record is retained here for purposes of transparency. If you have any questions, please contact the corresponding author. The correct preprint can be found at doi: 10.1101/2024.07.18.604071

microbiology↗

bioRxiv2024

The role of stomatin-like protein (STOML) in Plasmodium falciparum

Members of the Stomatin, Prohibitin, Flotillin and HflK/C (SPFH) protein family form large membrane anchored or spanning complexes and are involved in various functions in different organelles. The human malaria causing parasite Plasmodium falciparum harbors four SPFH proteins, including prohibitin 1 and 2, prohibitin-like protein (PHBL), and stomatin-like protein (STOML), which all localize to the parasite mitochondrion. In the murine model parasite Plasmodium berghei, STOML appears essential for asexual blood-stage (ABS) development and is localized to puncta on mitochondrial branching points in oocyst stages. In this study, we show that deletion of STOML causes a significant growth defect and slower ABS development, while sexual-stage development remains unaffected. Parasites lacking STOML were not more sensitive to respiratory chain targeting drugs, rendering a function of STOML in respiratory chain assembly unlikely. Epitope tagging of endogenous STOML revealed a distinct punctate localization on branching points and endings of the ABS mitochondrial network. STOML resides in a large protein complex and pulldown experiments identified a zinc dependent metalloprotease, FtsH, as a likely interaction partner. The predicted AlphaFold2 structure of STOML shows high similarity with the bacterial HflK/C, which has been shown to form a large vault-like structure around bacterial FtsH hexamers. Combined, our results suggest that a similar STOML-FtsH complex localized to specific loci of P. falciparum mitochondria facilitate the parasites ABS development.

microbiology↗

bioRxiv2024

Detailing organelle division and segregation in Plasmodium falciparum

The malaria causing parasite, Plasmodium falciparum, replicates through a tightly orchestrated process termed schizogony, where approximately 32 daughter parasites are formed in a single infected red blood cell and thousands of daughter cells in mosquito or liver stages. One-per-cell organelles, such as the mitochondrion and apicoplast, need to be properly divided and segregated to ensure a complete set of organelles per daughter parasites. Although this is highly essential, details about the processes and mechanisms involved remain unknown. We developed a new reporter parasite line that allows visualization of the mitochondrion in blood and mosquito stages. Using high-resolution 3D-imaging, we found that the mitochondrion orients in a cartwheel structure, prior to stepwise, non-geometric division during the last stage of schizogony. Analysis of focused ion beam scanning electron microscopy (FIB-SEM) data confirmed these mitochondrial division stages. Furthermore, these data allowed us to elucidate apicoplast division steps, highlighted its close association with the mitochondrion, and showed putative roles of the centriolar plaques (CPs) in apicoplast segregation. These observations form the foundation for a new detailed mechanistic model of mitochondrial and apicoplast division and segregation during P. falciparum schizogony and pave the way for future studies into the proteins and protein complexes involved in organelle division and segregation.

microbiology↗

bioRxiv2023

Comparative 3D ultrastructure of Plasmodium falciparum gametocytes

Despite the enormous significance of malaria parasites for global health, some basic features of their ultrastructure remain obscure. In this study, we apply high-resolution volumetric electron microscopy to examine and compare the ultrastructure of Plasmodium falciparum gametocytes of both genders and in different stages of development as well as the more intensively studied asexual blood stages revisiting previously described phenomena in 3D. In doing so, we challenge the widely accepted notion of a single mitochondrion by demonstrating the presence of multiple mitochondria in gametocytes. We also provide evidence for a gametocyte-specific cytostome variant. Furthermore, we generate, among other organelles, the first 3D reconstructions of endoplasmic reticulum (ER), Golgi apparatus, and extraparasitic structures in gametocytes. Assessing interconnectivity between organelles, we find frequent structural appositions between the nucleus, mitochondria, and apicoplast. We provide evidence that the ER is a promiscuous interactor with numerous organelles and the trilaminar membrane of the gametocyte. Public availability of these volumetric electron microscopy resources of wild-type asexual and sexual blood-stage malaria parasites will facilitate reinterrogation of this global dataset with different research questions and expertise. Taken together, we reconstruct the 3D ultrastructure of P. falciparum gametocytes in high detail and shed light on the unique organellar biology of these deadly parasites.

microbiology↗

bioRxiv2021

A revised mechanism for how Plasmodium falciparum recruits and exports proteins into its erythrocytic host cell.

Plasmodium falciparum exports ~10% of its proteome into its host erythrocyte to modify the host cells physiology. The Plasmodium export element (PEXEL) motif contained within the N-terminus of most exported proteins directs the trafficking of those proteins into the erythrocyte. To reach the host cell, the PEXEL motif of exported proteins are processed by the endoplasmic reticulum (ER) resident aspartyl protease plasmepsin V. Then, following secretion into the parasite-encasing parasitophorous vacuole, the mature exported protein must be unfolded and translocated across the parasitophorous vacuole membrane by the Plasmodium translocon of exported proteins (PTEX). PTEX is a protein-conducting channel consisting of the pore-forming protein EXP2, the protein unfoldase HSP101, and structural component PTEX150. The mechanism of how exported proteins are specifically trafficked from the parasites ER following PEXEL cleavage to PTEX complexes on the parasitophorous vacuole membrane is currently not understood. Here, we present evidence that EXP2 and PTEX150 form a stable subcomplex that facilitates HSP101 docking. We also demonstrate that HSP101 localises both within the parasitophorous vacuole and within the parasites ER throughout the ring and trophozoite stage of the parasite, coinciding with the timeframe of protein export. Interestingly, we found that HSP101 can form specific interactions with model PEXEL proteins in the parasite ER, irrespective of their PEXEL processing status. Collectively, our data suggest that HSP101 recognises and chaperones PEXEL proteins from the ER to the parasitophorous vacuole and given HSP101s specificity for the EXP2-PTEX150 subcomplex, this provides a mechanism for how exported proteins are specifically targeted to PTEX for translocation into the erythrocyte. Author SummaryPlasmodium falciparum, the most lethal species of human malaria parasite, infects erythrocytes and develops within a parasitophorous vacuole. To support rapid parasite growth and immune evasion, the parasite remodels its erythrocyte by exporting a myriad of proteins into the erythrocyte compartment. Parasite proteins destined for export are first imported into the endoplasmic reticulum (ER) and then secreted into the parasitophorous vacuole, where they are translocated across the parasitophorous vacuole membrane into the erythrocyte via a protein-conducting channel called PTEX. A missing link in the story has been how proteins destined for export are specifically guided from the ER to PTEX at the parasitophorous vacuole membrane. In this study, we found that one of the core PTEX components, HSP101, resides within the parasites ER, in addition to its PTEX-related location at the parasitophorous vacuole. We also found that ER-located HSP101 can interact transiently with cargo proteins en route to the parasitophorous vacuole membrane. Our findings support a model in which HSP101 forms an initial interaction with exported proteins in the ER and then chaperones them to the rest of PTEX at the parasitophorous vacuole membrane for export into the erythrocyte.

microbiology↗

bioRxiv2021

A prioritized and validated resource of mitochondrial proteins in Plasmodium identifies leads to unique biology

Plasmodium species have a single mitochondrion that is essential for their survival and has been successfully targeted by anti-malarial drugs. Most mitochondrial proteins are imported into this organelle and our picture of the Plasmodium mitochondrial proteome remains incomplete. Many data sources contain information about mitochondrial localization, including proteome and gene expression profiles, orthology to mitochondrial proteins from other species, co-evolutionary relationships, and amino acid sequences, each with different coverage and reliability. To obtain a comprehensive, prioritized list of Plasmodium falciparum mitochondrial proteins, we rigorously analyzed and integrated eight datasets using Bayesian statistics into a predictive score per protein for mitochondrial localization. At a corrected false discovery rate of 25%, we identified 445 proteins with a sensitivity of 87% and a specificity of 97%. They include proteins that have not been identified as mitochondrial in other eukaryotes but have characterized homologs in bacteria that are involved in metabolism or translation. Mitochondrial localization of seven Plasmodium berghei orthologs was confirmed by epitope labeling and co-localization with a mitochondrial marker protein. One of these belongs to a newly identified apicomplexan mitochondrial protein family that in P. falciparum has four members. With the experimentally validated mitochondrial proteins and the complete ranked P. falciparum proteome, which we have named PlasmoMitoCarta, we present a resource to study unique proteins of Plasmodium mitochondria.

bioinformatics↗