A break in mitochondrial endosymbiosis as a basis for inflammatory diseases

This is a hybrid event - with the speaker attending in-person and viewable on Teams.

The endosymbiotic origin of mitochondria means that within our cells we host hundreds of organelles that retain many aspects of their bacterial origin which must be tolerated. Consequently, the release of mitochondrial factors into the cytosol can trigger cell death, innate immunity and inflammation. A range of findings in immunometabolism have revealed how mitochondria are an important source of factors that promote immunity and inflammation. These include mitochondrial nucleic acids that can be sensed by innate sensors such as cGAS and MDA-5, metabolites such as succinate, fumarate and itaconate, that have a range of effects, with itaconate in particular being anti-inflammatory. Recent work from my lab has uncovered a role of fumarate hydratase in driving the release of mitochondrial double-stranded RNA, and a role of reactive oxygen species made by Complex III in the electron transport chain as being key for IL10 induction. Since mitochondrial change appears critical for inflammation, it could be that environmental factors, including obesity, pathogens or toxins, might promote a breakdown in endosymbiosis. This could be part of why the incidence of autoimmune disease has increased substantially over the past 50 years or so.