Mitochondrial division in T. gondii: analysis of the Dynamin-related protein C and of its putative interactors

QH Natural history

Melatti, Carmen ; Meissner, Markus

University:University of Glasgow

Department:Institute of Infection Immunity and Inflammation

关键词: Toxoplasma gondii, mitochoondria, division, cytoskeleton, cell cycle, parasite.;   

Others  :  http://theses.gla.ac.uk/38972/1/2018MelattiPhD.pdf

来源: University of Glasgow

【 摘 要 】

Apicomplexa parasites such as Plasmodium spp. and Toxoplasma gondii are characterised by a single, lasso-shaped mitochondrion. This organelle is critical during all phases of the parasite life cycle, and is a validated drug target against parasites of the Apicomplexa phylum. In contrast to other eukaryotes, replication of the mitochondrion in these parasites is tightly linked to the cell cycle. A key step in mitochondrial segregation is the fission event, which in many eukaryotes requires the action of Dynamin-related proteins: these mechanochemical enzymes are recruited at the outer membrane of the mitochondria and mediate membrane constriction. To date, none of the components of the apicomplexan fission machinery have been identified and validated. In this work, I investigated the role of DrpC, a highly divergent, Apicomplexa-specific putative Dynamin-related protein, in T. gondii. Endogenous tagging showed that DrpC is adjacent to the mitochondrion, and is localised both at its periphery and at its basal part, where fission is expected to occur. Depletion and dominant negative expression of DrpC results in interconnected mitochondria and ultimately in drastic changes in mitochondrial morphology, leading to parasite death. These data indicate that DrpC is essential for mitochondrial biogenesis in T. gondii. To better understand the fission mechanism, DrpC potential interactors were investigated in this study; intriguingly, it is here shown that the conserved mitochondrial protein Fis1, which in other eukaryotes recruits the Dynamin-related protein during fission, is not required for mitochondrial fission in T. gondii. Conversely, immunoprecipitation data suggest an interaction between DrpC and the microtubule scaffold; as DrpC is also seen at the periphery of the parasite, these data could suggest a second role for this atypical Dynamin-related protein.