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Tassan-Lugrezin, S.

Publications and source records attributed to Tassan-Lugrezin, S..

3 recordsLinked to original sources

Streamlining large-scale high-resolution electron tomography with VolWeaver

Researchers using electron microscopy must often balance a trade-off between obtaining high-resolution structural information and preserving sufficient cellular context. At one end of this spectrum, single particle cryo-electron microscopy and cryo-electron tomography provide near-molecular detail but are typically limited to relatively small fields of view. At the other, volume electron microscopy approaches, such as scanning electron microscopy of resin-embedded specimens, capture large cellular volumes but generally at lower resolution. Consequently, linking nanoscale structural information to larger cellular architecture remains a significant challenge. To address this gap, we optimised a transmission electron tomography workflow for resin-embedded malaria parasites that allows us to visualise targeted regions of interest at nanometre-scale resolution while retaining several micrometres of surrounding cellular context. Here, we present our current best-practice pipeline for sample preparation, tomogram acquisition, and reconstruction. In addition, we introduce VolWeaver, a data-processing framework, that integrates high-resolution tomographic datasets into serial section volume reconstructions, enabling the visualisation and interpretation of ultrastructural features within their broader cellular environment.

cell biology↗

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↗

Building without the architect: the dispensable role of MICOS in de novo cristae formation in malaria parasites

The malaria parasite mitochondria represent the only tractable, naturally occurring system in which cristae, the characteristic invaginations of the inner mitochondrial membrane, are known to be formed de novo. In traditional model organisms, the central complex involved in cristae organization is the mitochondrial contact site and cristae organizing system (MICOS). However, whether MICOS has an active role in the initial formation of cristae remains unclear. We identified two putative Plasmodium falciparum MICOS components, PfMIC19 and PfMIC60 and show that both genes are dispensable in asexual blood stages, gametocytes, and mosquito stages, albeit with a mild reduction in oocyst numbers. Immunofluorescence microscopy and electron tomography of gametocytes lacking either or both MICOS orthologues showed aberrant mitochondrial morphology and abnormal cristae, with a marked reduction of crista junctions. Thus, by utilizing the unique properties of P. falciparum, we confirmed the involvement of PfMIC19 and PfMIC60 in the organization of crista junctions, while providing evidence that MICOS is not required for the initial formation of cristae.

microbiology↗