A new study has identified a significant link between fumarate, a mitochondrial metabolite, and the activation of inflammatory responses that may contribute to cancer and autoimmune diseases. Researchers developed mouse and cell models to explore the effects of fumarate accumulation, discovering that this accumulation causes mitochondrial damage, which releases mitochondrial DNA (mtDNA) and RNA (mtRNA) in small vesicles. This release triggers an immune response and results in inflammation. Specifically, the absence of fumarate hydratase (FH) in the Krebs cycle leads to increased fumarate levels, associated with a severe form of kidney cancer. The study, led by Professor Christian Frezza and published in Nature, demonstrates for the first time the correlation between mitochondrial metabolites and inflammation onset, potentially paving the way for innovative cancer treatments. Additionally, a collaborative research group in Dublin, led by Professor Luke O’Neill, found a similar mechanism in macrophages, where released mtRNA is a key trigger of inflammation. The research was supported by various funding bodies, including Cancer Research UK and the European Research Council, highlighting its importance in understanding the intersection of mitochondrial function, inflammation, and cancer pathology.
