Date Published: April 4, 2019
Publisher: Public Library of Science
Author(s): Carmen Melatti, Manuela Pieperhoff, Leandro Lemgruber, Ehmke Pohl, Lilach Sheiner, Markus Meissner, Kami Kim.
The single mitochondrion of apicomplexan protozoa is thought to be critical for all stages of the life cycle, and is a validated drug target against these important human and veterinary parasites. In contrast to other eukaryotes, replication of the mitochondrion is tightly linked to the cell cycle. A key step in mitochondrial segregation is the fission event, which in many eukaryotes occurs by the action of dynamins constricting the outer membrane of the mitochondria from the cytosolic face. To date, none of the components of the apicomplexan fission machinery have been identified and validated. We identify here a highly divergent, dynamin-related protein (TgDrpC), conserved in apicomplexans as essential for mitochondrial biogenesis and potentially for fission in Toxoplasma gondii. We show that TgDrpC is found adjacent to the mitochondrion, and is localised both at its periphery and at its basal part, where fission is expected to occur. We demonstrate that depletion or dominant negative expression of TgDrpC results in interconnected mitochondria and ultimately in drastic changes in mitochondrial morphology, as well as in parasite death. Intriguingly, we find that the canonical adaptor TgFis1 is not required for mitochondrial fission. The identification of an Apicomplexa-specific enzyme required for mitochondrial biogenesis and essential for parasite growth highlights parasite adaptation. This work paves the way for future drug development targeting TgDrpC, and for the analysis of additional partners involved in this crucial step of apicomplexan multiplication.
Members of the Apicomplexa phylum are unicellular obligate parasites. Being eukaryotes, they share many features of common model organisms, such as a double-membrane nuclear envelope and a conserved endomembrane system. However, they are also set apart by various novel characteristics, such as the phylum-specific apical complex, which contains specialised secretory organelles; a pellicle-like membranous compartment called the inner membrane complex (IMC); and an atypical non-photosynthetic plastid, the apicoplast.
Mitochondrial fission is crucial for the control of organelle morphology and function. Here, we investigated the role in T. gondii of conserved components of the fission machinery.