A mitochondrial protein affects cell morphology, mitochondrial segregation and virulence in Leishmania

Uboldi, AD; Lueder, FB; Walsh, P; Spurck, T; McFadden, GI; Curtis, J; Likic, VA; Perugini, MA; Barson, M; Lithgow, T; Handman, E

Author(s): Uboldi, AD; Lueder, FB; Walsh, P; Spurck, T; McFadden, GI; Curtis, J; Likic, VA; Perugini, MA; Barson, M; Lithgow, T; Handman, E;
Details: Publication Year 2006-12,Volume 36,Issue #14,Page 1499-1514
Journal Title: INTERNATIONAL JOURNAL FOR PARASITOLOGY
Publication Type: Journal Article
Abstract: The single mitochondrion of kinetoplastids divides in synchrony with the nucleus and plays a crucial role in cell division. However, despite its importance and potential as a drug target, the mechanism of mitochondrial division and segregation and the molecules involved are only partly understood. In our quest to identify novel mitochondrial proteins in Leishmania, we constructed a hidden Markov model from the targeting motifs of known mitochondrial proteins as a tool to search the Leishmania major genome. We show here that one of the 17 proteins of unknown function that we identified, designated mitochondrial protein X (MIX), is an oligomeric protein probably located in the inner membrane and expressed throughout the Leishmania life cycle. The MIX gene appears to be essential. Moreover, even deletion of one allele from L. major led to abnormalities in cell morphology, mitochondrial segregation and, importantly, to loss of virulence. MIX is unique to kinetoplastids but its heterologous expression in Saccharomyces cerevisiae produced defects in mitochondrial morphology. Our data show that a number of mitochondrial proteins are unique to kinetoplastids and some, like MIX, play a central role in mitochondrial segregation and cell division, as well as virulence. (c) 2006 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.
Publisher: PERGAMON-ELSEVIER SCIENCE LTD
Keywords: INDUCED PHASE-SEPARATION; DYNAMIN-RELATED GTPASE; HIDDEN MARKOV-MODELS; TRYPANOSOMA-BRUCEI; MEMBRANE-PROTEINS; KINETOPLAST DNA; TRITON X-114; CRITHIDIA-FASCICULATA; INNER MEMBRANE; IN-VIVO
Publisher's Version: https://doi.org/10.1016/j.ijpara.2006.08.006
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2006-12-01 12:00:00