Skip to main content

Research Repository

Advanced Search

A unique dynamin-related protein is essential for mitochondrial fission in Toxoplasma gondii

Melatti, Carmen; Pieperhoff, Manuela; Lemgruber, Leandro; Pohl, Ehmke; Sheiner, Lilach; Meissner, Markus

A unique dynamin-related protein is essential for mitochondrial fission in Toxoplasma gondii Thumbnail


Authors

Carmen Melatti

Manuela Pieperhoff

Leandro Lemgruber

Lilach Sheiner

Markus Meissner



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.

Citation

Melatti, C., Pieperhoff, M., Lemgruber, L., Pohl, E., Sheiner, L., & Meissner, M. (2019). A unique dynamin-related protein is essential for mitochondrial fission in Toxoplasma gondii. PLoS Pathogens, 15(4), Article e1007512. https://doi.org/10.1371/journal.ppat.1007512

Journal Article Type Article
Acceptance Date Dec 10, 2018
Online Publication Date Apr 4, 2019
Publication Date Apr 4, 2019
Deposit Date Apr 10, 2019
Publicly Available Date Apr 10, 2019
Journal PLoS Pathogens
Print ISSN 1553-7366
Electronic ISSN 1553-7374
Publisher Public Library of Science
Peer Reviewed Peer Reviewed
Volume 15
Issue 4
Article Number e1007512
DOI https://doi.org/10.1371/journal.ppat.1007512

Files

Published Journal Article (3.5 Mb)
PDF

Publisher Licence URL
http://creativecommons.org/licenses/by/4.0/

Copyright Statement
© 2019 Melatti et al. This is an open
access article distributed under the terms of the
Creative Commons Attribution License, which
permits unrestricted use, distribution, and
reproduction in any medium, provided the original
author and source are credited.







You might also like



Downloadable Citations