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Durham University

Department of Biosciences

Profile

Publication details for Prof. Ehmke Pohl

Melatti, Carmen, Pieperhoff, Manuela, Lemgruber, Leandro, Pohl, Ehmke, Sheiner, Lilach & Meissner, Markus (2019). A unique dynamin-related protein is essential for mitochondrial fission in Toxoplasma gondii. PLoS Pathogens 15(4): e1007512.

Author(s) from Durham

Abstract

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.