New Insights into the Role that Mitochondria Play in Killing Bacteria
Mitochondria shown to assist the immune system by delivering reactive oxygen species to macrophages.
Mitochondria are often thought of as the energy providers of the cell, however research from Michigan Medicine suggests that they may play important roles in fighting bacteria too.
Reactive Oxygen Species (ROS) are a byproduct of oxygen metabolism in the mitochondria. These produce well-known toxic effects such as the initiation of cancer formation, diabetes, and aging (Di Meo et al, 2016). Along with these negative effects, ROS is also used by macrophages to kill bacteria.
When harmful bacteria enters the body, the immune response starts by targeting macrophages to engulf it, isolating the bacteria and preventing it from causing harm. Once this is complete, the macrophage begins to use various methods to destroy it. One of the ways this is accomplished is through the use of ROS. When a macrophage engulfs bacteria, phagocyte oxidase multi-protein complex (NOX2) is recruited and produces ROS.
Many pathogens such as Methicillin-resistant Staphylococcus aureus (MRSA), however, inhibit this process.
The researchers of the current study aimed to discover whether mitochondria ROS production also contributes to the immune response. To do this, they observed ROS production in MRSA-infected macrophages using MitoPY -- a probe that fluoresces in response to ROS. When the outside of the cell was exposed to MRSA, MitoPY florescence was restricted to within the mitochondria. Once the bacteria had been engulfed by the cell however, fluorescence was observed outside of the mitochondria
To researchers also studied the effects of inhibiting mitochondrial ROS production on the macrophage's ability to fight infection. CRISPR CAS-9 was employed to create macrophages lacking the protein IRE1α, a stress-sensing protein in the endoplasmic reticulum. These cells exhibited decreased ROS production in mitochondria, along with a decreased ability to kill MRSA bacteria.
Together, these results suggest that mitochondria contribute significantly to the macrophage ROS-dependent bacteria destruction process. With ROS production beginning in the mitochondria and subsequently transported to the rest of the macrophage once endocytosis occurs.