PROJECT SUMMARY/ABSTRACT
Inter-organellar communication is an essential process for cellular function. Inside the cell, organelles can
interact through specialized microdomains called membrane contact sites (MCSs). These structures mediate the
close apposition of two organellar membranes, allowing the exchange of metabolites. In doing so, MCSs are
crucial for cellular homeostasis and metabolic plasticity. However, most of what is known about MCSs comes
only from a handful of well-studied metazoans, particularly yeast and mammals. Studying the function and
composition of MCSs in other eukaryotes—particularly in divergent lineages possessing phylum-specific
organelles—is therefore crucial to gain insights into the mechanisms requiring an independent solution to inter-
organellar communication.
My group seeks to understand inter-organellar communication in apicomplexans, are a group of parasitic protists
that include the causative agents of malaria and toxoplasmosis. In their complex life cycles, many of these
organisms transition through a variety of environments as they enter and exit cells in different host species. The
ability to propagate within a wide range of cell types relies on the capacity to access nutrients from diverse and
changing environments, which underscores the metabolic plasticity of apicomplexans. Most apicomplexans
possess a single mitochondrion and an apicoplast, a non-photosynthetic plastid that arose from a secondary
endosymbiotic event at least 600 million years ago. Both organelles have been coevolving ever since, and now
play crucial roles in the metabolic plasticity and survival of these parasites. Although a close physical interaction
between the mitochondrion and the apicoplast has been observed, the molecular identity of this interaction
remains elusive.
Using the model apicomplexan Toxoplasma gondii, my laboratory aims to identify the molecular effectors
mediating the mitochondrion-apicoplast interaction using two different, yet complementary approaches:
proximity biotinylation and bimolecular complementation. As the apicoplast is an apicomplexan-specific
organelle, the identification of proteins involved in mitochondrion-apicoplast MCSs could provide opportunities
for the design of anti-parasitic therapies against these pathogens. Our work will open new scientific venues of
apicomplexan biology, and yield insight into the evolution and organellar crosstalk in these organisms.