Mitocurcumin mediated redox disruption and metabolic rewiring induces tumor regression in Drosophila intestinal stem cell tumors

Mitocurcumin, a mitochondria-targeted molecule, has been shown to effectively reduce tumor growth in Drosophila intestinal stem cell tumors. Researchers employed an integrated approach, combining molecular modeling and in vivo experiments, to identify thioredoxin reductase (TrxR) as a crucial redox target of Mitocurcumin. Molecular simulations demonstrated a stable interaction between Mitocurcumin and both Drosophila and mammalian TrxR homologs.

Upon treatment with Mitocurcumin, the study observed a decrease in mitotic activity, increased reactive oxygen species (ROS) levels within a specific intestinal stem cell population, enhanced apoptosis in the tumor-bearing guts, and significant mitochondrial membrane depolarization. Despite the impairment of mitochondrial function, the overall mitochondrial morphology remained largely unaltered, pointing to a primary disruption of redox buffering rather than structural collapse.

Metabolomic analysis revealed a remodeling of energy metabolism as the gut reacted to oxidative stress. Remarkably, the treatment not only alleviated the swelling caused by the tumors but also extended the lifespan of the flies, suggesting a systemic and organism-wide response to Mitocurcumin treatment. The study underscores the potential of Drosophila as a valuable model for evaluating the effects of mitochondria-targeted bioactive molecules.