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, immune and cell death signaling. With such diverse cellular roles, it is no surprise that virulence factors of both bacterial and viral origin target mitochondria during infection.
Coxiella burnetii is a unique intracellular bacterial pathogen and the causative agent of Q fever. The bacterium infects alveolar macrophages and replicates within a 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 translocated into the cell modulate cellular functions to facilitate CCV development and bacterial replication.
Mitochondrial function is highly dependent on it’s proteome and so to gain a more holistic insight into the impact of C. burnetii infection on this organelle, we utilised Stable Isotope Labeling of Amino Acids in Cell culture and proteomically compared mitochondria isolated from uninfected and C. burnetii-infected THP-1 macrophages following 3-days infection by mass spectrometry. This identified over 800 mitochondrial proteins, more than 150 of which were significantly changed in abundance during infection. Intriguingly, these proteins participate in multiple mitochondrial pathways, indicating a global effect on the mitochondria in response to C. burnetii infection. Oxidative phosphorylation appeared most affected, with a large number of respiratory complex I proteins affected. In addition, proteins connected to mitochondrial translation, fatty acid oxidation, the tricarboxylic acid (TCA) cycle and glutamate metabolism were also altered in infected cells. These findings indicate that the host cell mitochondria is modified during intracellular infection and whether these changes are host-derived or bacterial directed will be the focus of further research.