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Browsing by Author "Oliveira Souza, Rodolpho Ornitz"
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Item IMC10 and LMF1 mediate mitochondrial morphology through mitochondrion-pellicle contact sites in Toxoplasma gondii(The Company of Biologists, 2022) Oliveira Souza, Rodolpho Ornitz; Jacobs, Kylie N.; Back, Peter S.; Bradley, Peter J.; Arrizabalaga, Gustavo; Pharmacology and Toxicology, School of MedicineThe single mitochondrion of Toxoplasma gondii is highly dynamic, being predominantly in a peripherally distributed lasso-shape in intracellular parasites and collapsed in extracellular parasites. The peripheral positioning of the mitochondrion is associated with apparent contacts between the mitochondrion membrane and the parasite pellicle. The outer mitochondrial membrane-associated protein LMF1 is critical for the correct positioning of the mitochondrion. Intracellular parasites lacking LMF1 fail to form the lasso-shaped mitochondrion. To identify other proteins that tether the mitochondrion of the parasite to the pellicle, we performed a yeast two-hybrid screen for LMF1 interactors. We identified 70 putative interactors localized in different cellular compartments, such as the apical end of the parasite, mitochondrial membrane and the inner membrane complex (IMC), including with the pellicle protein IMC10. Using protein-protein interaction assays, we confirmed the interaction of LMF1 with IMC10. Conditional knockdown of IMC10 does not affect parasite viability but severely affects mitochondrial morphology in intracellular parasites and mitochondrial distribution to the daughter cells during division. In effect, IMC10 knockdown phenocopies disruption of LMF1, suggesting that these two proteins define a novel membrane tether between the mitochondrion and the IMC in Toxoplasma. This article has an associated First Person interview with the first author of the paper.Item Protein control of membrane and organelle dynamics: Insights from the divergent eukaryote Toxoplasma gondii(Elsevier, 2022) Ovciarikova, Jana; Oliveira Souza, Rodolpho Ornitz; Arrizabalaga, Gustavo; Sheiner, Lilach; Pharmacology and Toxicology, School of MedicineIntegral membrane protein complexes control key cellular functions in eukaryotes by defining membrane-bound spaces within organelles and mediating inter-organelles contacts. Despite the critical role of membrane complexes in cell biology, most of our knowledge is from a handful of model systems, primarily yeast and mammals, while a full functional and evolutionary understanding remains incomplete without the perspective from a broad range of divergent organisms. Apicomplexan parasites are single-cell eukaryotes whose survival depends on organelle compartmentalisation and communication. Studies of a model apicomplexan, Toxoplasma gondii, reveal unexpected divergence in the composition and function of complexes previously considered broadly conserved, such as the mitochondrial ATP synthase and the tethers mediating ER-mitochondria membrane contact sites. Thus, Toxoplasma joins the repertoire of divergent model eukaryotes whose research completes our understanding of fundamental cell biology.