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Access Type
WSU Access
Date of Award
January 2025
Degree Type
Thesis
Degree Name
M.S.
Department
Biochemistry and Molecular Biology
First Advisor
Maik Hüttemann
Abstract
Cytochrome c Oxidase (CcO) is the terminal enzyme of the electron transport chain in mammals and is subject to tight regulation. We here analyzed heart mitochondria from Cohen diabetes-resistant (CDr) and diabetes-sensitive (CDs) rats, a model for type 2 diabetes. We uncovered a specific inhibitory phosphorylation at tyrosine 304 on the catalytic subunit I of CcO (pY304-CcO-I) induced by a high-sucrose diet in CDr and CDs rats. This phosphorylation is found in dimeric CcO and, for the first time, in a specific subset of respiratory supercomplexes (SCs), which is linked to increased tissue inflammation and reduced CcO activity, causing mitochondrial impairment and contributing to overall metabolic dysfunction. We propose that CcO enzymatic activity in dimeric CcO and specific CcO-associated SCs is regulated through Y304-CcO-I phosphorylation, leading to enzyme inhibition, redistribution of SCs, and diminished mitochondrial quality control. These results suggest that the combination of genetic predisposition to diabetes and high-sucrose diet is most detrimental to cardiac health.
Recommended Citation
Pavelich, Lauren, "Regulation Of Respiratory Supercomplexes Through Inhibitory Cytochrome C Oxidase Y304 Phosphorylation Causes Mitochondrial Dysfunction In Diabetic Heart" (2025). Wayne State University Theses. 1008.
https://digitalcommons.wayne.edu/oa_theses/1008