A report published by Hooftman et al in Nature established that the tricarboxylic acid cycle enzyme fumarate hydratase is repressed in macrophages and also found that cells from patients with systemic lupus erythematosus also exhibited suppression of fumarate hydratase. In a companion press release on the findings from Trinity College Dublin, coauthors on the study commented, “No one has made a link from fumarate hydratase to inflammatory macrophages before, and we feel that this process might be targetable to treat debilitating diseases like lupus.... We found that when fumarate hydratase is repressed, RNA is released from mitochondria, which can bind to key proteins MDA5 and TLR7 and trigger the release of cytokines, thereby worsening inflammation. Restoring fumarate hydratase in these diseases or targeting MDA5 or TLR7 therefore presents an exciting prospect for badly needed new anti-inflammatory therapies.”
May 25, 2023