Mitochondrial contribution to innate immune pathways

 

The ability of cells in the body to recognize bacteria and viruses is critical to survival. Depending on the type of infection, the cell will activate different pathways that generally lead to two distinct responses; first, the cell will secrete proteins called cytokines that alert neighbouring cells to the infection, particularly cells of the immune system. Second, a series of events are triggered to shut down the replication of the pathogen inside the cell. This direct cellular response to infection is called “innate immunity”.

Over the past few years, researchers have identified a critical role for an intracellular organelle, called mitochondria, in the propagation of these signals. Mitochondria are well known as the “energy powerhouse of the cell”, however, they can also act as a platform to assemble anti-viral and anti-inflammatory signalling. In addition, mitochondria still retain bacterial signatures, including their own unmethylated DNA, as well as the machinery to translate proteins.

It was recently shown that this mitochondrial DNA is released into the cell cytoplasm under certain stress conditions. When this happens, the cellular antiviral responses are initiated, as if the cell was infected with bacteria. In this way, mitochondria play a central role as both a signalling platform to launch the protective response to infection, and as a direct activator of this response when their own DNA is released. This project aims to investigate the role of mitochondria in innate immune responses and to develop a detailed understanding of how mitochondria control innate immune signalling pathways.

The project is led in Canada by the Montreal Neurological Institute – McGill University in collaboration with the Weizmann Institute (Israel), Universidad Andres Bello (Chile), and the National Institute of Biological Sciences (China). It was selected and approved for funding through the second research competition of the Joint Canada-Israel Health Research Program, which is a partnership between Canada’s International Development Research Centre, the Canadian Institutes for Health Research, the Israel Science Foundation and the Azrieli Foundation. This seven-year, $35M Canadian-Israeli effort draws on the unique scientific strengths of both countries and facilitates networking opportunities with peers from Africa, Asia, and Latin America. All projects include a plan for integrating researchers from low- and middle-income countries that will establish long-term scientific relationships.