Objective: To determine whether loss of Mblac1, a gene implicated in copper metabolism and Alzheimer’s disease, causes systemic mitochondrial redox imbalance and whether treatment with the copper chaperone elesclomol (ES) can restore this balance. Methods: We employed 3D cryo-fluorescence imaging to quantify RR in kidneys and livers of Mblac1 KO mice and their wildtype (WT) littermates. Adult mice of both sexes were administered either vehicle control (C) or ES (10 mg/kg, i.p.). Results: KO tissues exhibited reduced RR values, indicating an oxidized metabolic state. ES treatment recovered 77 % of the RR deficit in kidneys and 48 % in livers, restoring RR to WT levels. Conclusion: Mblac1 deletion disrupts mitochondrial redox homeostasis in peripheral tissues, while ES partially reverses this imbalance by restoring Cu(I)-dependent metabolism. Significance: Optical metabolic imaging reveals Mblac1 as a key regulator of systemic redox balance and supports ES as a potential therapy for Cu-linked metabolic dysfunctions.

Significance: Endothelial c-Myc plays a critical role in redox homeostasis, with its deletion potentially exacerbating oxidative stress, particularly during chemotherapy. Aim: To assess the metabolic impact of endothelial c-Myc knockout (KO) and doxorubicin (DOXO) treatment on kidneys, hearts, and livers using 3D optical cryo-imaging. Approach: Redox ratios (NADH/FAD) were analyzed in control (CT) and KO mice treated with DOXO or saline to evaluate mitochondrial function and oxidative states. Results: KO tissues showed significant reductions in redox ratios, indicating an oxidized state, with kidneys exhibiting up to a 51.42% decrease. DOXO treatment further exacerbated oxidative stress in KO tissues, while CT groups demonstrated protective effects. Conclusions: Endothelial c-Myc is crucial for redox balance and protection against chemotherapy-induced oxidative damage, offering insights for targeted therapeutic strategies.

Metformin hydrochloride, an antihyperglycemic agent, and sulindac, a nonsteroidal anti-inflammatory drug, are FDA-approved drugs known to exert anticancer effects. Previous studies demonstrated sulindac and metformin’s anticancer properties through mitochondrial dysfunction and inhibition of mitochondrial electron transport chain (ETC) complex I, as well as key signaling pathways. In this study, various drugs were adminsitered to A549 lung cancer cells, and results revealed that a combination of sulindac and metformin enhanced cell death compared to administration of the drugs separately. To measure superoxide production over time, we employed a time-lapse fluorescence imaging technique using mitochondrial-targeted hydroethidine. Fluorescence microscopy data showed largest increases in superoxide production in the combination treatment of metformin and sulindac. Results showed significant differences between the combined drug treatment and control groups, as well as between the positive control and control groups. This approach can be utilized to quantify anticancer efficacy of drugs, creating possibilities for additional therapeutic options.