The role of mitochondria in infection and beyond
Mitochondria are organelles that play central role in important cellular processes such as cell signaling and apoptosis. In many cases, mitochondrial function is altered during infection with pathogenic microorganisms. Often observed are changes in metabolism, energy production and calcium transport, as well as loss of mitochondrial membrane potential and compromised mitochondrial integrity. Bacterial or viral proteins can also be imported into mitochondria, where they modulate mitochondrial function. In addition, some intracellular-residing bacteria and parasites are known to recruit mitochondria to the surface of their infection vacuole, although the purpose of this remains undetermined. This project aims to understand the complexity and importance of the interaction between pathogenic microorganisms and mitochondria.
To be able to study this interaction, we have created a collection of inducible, siRNA-based cell lines where we can downregulate mitochondrial protein transport machineries, OXPHOS complexes or important metabolic proteins. Using these cell lines, we have addressed the transport pathway of PorBIA from Neisseria gonorrhoeae and Ats-1 from Anaplasma phagocytophilum and we are currently investigating the role of mitochondria in infection with intracellular pathogens Simkania negevensis and Chlamydia trachomatis.
The knockdown cell lines proved useful not only for studying interplay between microbes and mitochondria, but also for addressing fundamental questions about mitochondrial membrane biogenesis. Our work focuses in part on the mitochondrial intermembrane space bridging complex (MIB), a large protein complex that comprises the sorting and assembly machinery of the outer mitochondrial membrane (SAM) and the mitochondrial contact site and cristae organizing system (MICOS) in the inner mitochondrial membrane. The MIB complex is necessary for the maintenance of cristae morphology and we are currently exploring its structure and importance for other mitochondrial functions.