the MITOC THE POWERHOUSE AGAINST INFECTIOUS DISEASES
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itochondria are not just the powerhouse of the cell. Known for their role in energy production and metabolism, they also play a significant role in the immune system. While oxidative phosphorylation is the primary pathway of energy production in higher organisms, this process is oxygen-demanding and relatively slow under stressful conditions. Therefore, mitochondria can switch to glycolysis, a rapid energy-production method independent of oxygen supply. External stressors, like pathogen-specific metabolites, can also alter mitochondrial metabolism to favour pathogen survival and replication.
at the cellular level. They can transition from a catabolic, energy-producing phase to an anabolic phase to maximize the use of metabolites for both adenosine triphosphate (ATP) production (the cellular form of energy) and cellular homeostasis. Additionally, mitochondria generate reactive oxygen species (ROS) that activate inflammatory pathways within the cell to bolster protection against intracellular pathogens. ROS also activates essential immune cell subsets such as macrophages and T cells to control and clear extracellular pathogens. This article will explore the intricate interplay between mitochondrial metabolism and various bacterial and viral infections.
Notably, mitochondria can facilitate immune responses
MITOCHONDRIA AND BACTERIAL INFECTIONS
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egionnaire’s disease, a severe and potentially fatal bacterial pneumonia, is caused by Legionella pneumophila, an intracellular bacterium. Upon entry into human lung macrophages, L. pneumophila injects pathogenic proteins into the cell to initiate bacterial replication. This interaction has piqued great interest in better understanding Legionella infections since macrophages activation are largely influenced by mitochondrial metabolic responses. In 1983 L. pneumophila was observed to form Legionella-containing vacuoles (LCVs) upon entry into macrophages and later associate with the mitochondria. Recent studies have shed further light on how LCVs can cause mitochondrial fragmentation, an indicator of cell death. Mitochondrial fragmentation renders cells more susceptible to stressors and increases ROS production, where uncontrolled ROS output and oxidative stress can also induce cell death. Despite this, L. pneumophila did not induce other markers of cell death. Further analyses of macrophages’ metabolic rate after L. pneumophila infection revealed a shift from oxidative phosphorylation to glycolysis, a less sustainable option for long-term cell survival and energy production. One bacterial metabolite, which is injected
22 IMMpress Vol. 11 No. 2 2023
LEGIONNAIRE’S DISEASE
into cells upon macrophage entry, Ceg3, may interfere with a component of the oxidative phosphorylation pathway, potentially impacting ATP output and subsequent cellular function. Metabolic alterations that may favor glycolysis over oxidative phosphorylation resemble the Warburg effect observed in cancer cells, which allows for uncontrolled and deleterious cell division. Understanding the intricacies of this relationship between L. pneumophila infection and mitochondrial involvement provides valuable insights into the mechanisms of Legionnaire’s disease and potential avenues for therapeutic interventions.
