Mitochondria are essential organelles, fundamental to eukaryotic cell function and survival. Perhaps best known for their role in energy production, mitochondria are also central to many cellular processes, including calcium homeostasis, lipid metabolism, heme biosynthesis, immune signaling and apoptosis. With such diverse cellular roles, it is no surprise that an increasing number of pathogen virulence factors, of both bacterial and viral origin, are found to target the mitochondria during infection.
Coxiella burnetii is a unique intracellular bacterial pathogen and the causative agent of Q fever. The bacterium replicates within a highly acidic, lysosome-like vacuole, termed the Coxiella-containing vacuole (CCV). During infection, C. burnetii translocates over 130 bacterial effector proteins into the host cytosol via a Type 4 Secretion System (T4SS). Effector proteins secreted into the cell modulate a variety of cellular functions, facilitating CCV development and bacterial replication. Although the T4SS is essential for virulence, the contribution of the majority of C. burnetii effector proteins to bacterial pathogenesis remains uncharacterised.
The C. burnetii effector protein MceA is translocated into the host cell by the T4SS and displays specific localisation to the host cell mitochondria. Analysis of a MceA-deficient strain of C. burnetii revealed that the protein is not essential for CCV biogenesis or intracellular replication of the bacterium. Examination of MceA truncations demonstrated information encoded within the first two of four predicted transmembrane domains contains the targeting elements required for mitochondrial localisation of the protein. Isolation of mitochondria from C. burnetii infected cells revealed MceA localises to and is integrated into the outer mitochondrial membrane. Furthermore, the protein was found to interact with itself within a 120 kDa complex at this location. Collectively, these results highlight the mitochondria as a bona fide effector target during C. burnetii infection and ongoing research looks to elucidate the functional significance of mitochondrial targeting C. burnetii Dot/Icm effectors.