DEPARTMENT OF BIOLOGY, UNIVERSITY OF FRIBOURG, SWITZERLAND
DIVISION OF THE SINGLE MITOCHONDRION OF
TRYPANOSOMA BRUCEI
AND ITS IMPACT ON THE CELL CYCLE
Anne-Laure Chanez
Trypanosoma brucei is the parasite responsible of the transmission of human sleeping
sickness in Africa. Interestingly, this organism is one of the earliest diverging eukaryotes
with a bona fide mitochondrion. In contrast to most other eukaryotes, it has a single
mitochondrion only which shows a large network-like morphology. This unique feature
makes T. brucei an excellent model to study some unique aspects of mitochondrial biology.
First, we used T. brucei as a model to study the mechanisms of mammalian apoptosis.
Additionally to the one unit characteristic of its mitochondrion, the trypanosomes lack all
components of the “classical” apoptotic machinery. Because of these two unique features, we
were able to temporally separate the three major mitochondrial events that are induced by
Bax expression during apoptosis. First, cytochrome c is released from the mitochondrial
intermembrane space. This event is followed by a loss of the membrane potential and finally
by mitochondrial fragmentation. Interestingly, all these events are reversible when Bax is
removed.
Then we focused on the mechanism of division of the mitochondrion in T. brucei. The
proteins involved in this process are well conserved and two of them are found in the genome
of T. brucei. We have shown that the single dynamin-like protein (TbDLP), normally
specialized in mitochondrial fission, is not only involved in mitochondrial division, but also
required for endocytosis, a process normally mediated by classical dynamins which are
absent in T. brucei. The two specific intracellular localizations of TbDLP confirm the dual
function of this protein. Moreover, we showed that mitochondrial fission is required for the
completion of cytokinesis in T. brucei, suggesting that mitochondrial fission might be a
checkpoint for cell division. On the other hand, we have also identified the putative Fis1
homologue of T. brucei.
Generally in eukaryotes, the mitochondrial DNA is distributed all over the matrix. However
in T. brucei, it is restricted to a discrete structure termed the kinetoplast (or kDNA). Finally,
we have shown that TbMiX, a protein of the outer mitochondrial membrane, is essential for
the correct positioning of the kDNA. Moreover, we presented evidence that this protein may
link the mitochondrion to the subpellicular cytoskeleton of T. brucei, suggesting that the
microtubules present in this structure are required to determine the position of the kDNA.
Jury:
Prof. André Schneider, University of Fribourg (Director of Thesis)
Prof. Jean-Claude Martinou, University of Geneva (Expert)
Prof. Fritz Müller, University of Fribourg (President)