Elesclomol Diminishes Redox Imbalance in Peripheral Tissues of Mblac1 Knockout Mice
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Abstract
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.
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Abstract
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.
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Journal of Biophotonics
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Mehrnoosh Neghabi, Parisa Nategh, Anna M. Stauffer, et al.
Elesclomol Diminishes Redox Imbalance in Peripheral Tissues of Mblac1 Knockout Mice. Authorea. 31 October 2025.
DOI: https://doi.org/10.22541/au.176193932.29598629/v1
DOI: https://doi.org/10.22541/au.176193932.29598629/v1
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