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Access Type
WSU Access
Date of Award
January 2021
Degree Type
Dissertation
Degree Name
Ph.D.
Department
Physiology
First Advisor
Robert Wessells
Abstract
Cardiolipin (CL) is a phospholipid required for proper mitochondrial function. Tafazzin remodels CL to create highly unsaturated fatty acid chains. However, when tafazzin is mutated, CL remodeling is impeded, leading to mitochondrial dysfunction and the disease Barth syndrome. Patients with Barth syndrome often have severe exercise intolerance, which negatively impacts their overall quality of life. Boosting NAD+ levels can improve symptoms of other mitochondrial diseases, but its effect in the context of Barth syndrome has not been examined. We demonstrate for the first time that nicotinamide riboside (NR) can rescue exercise tolerance and mitochondrial respiration in a Drosophila tafazzin mutant and that the beneficial effects are dependent on sir2 and pgc-1α. Overexpressing pgc-1α increased the total abundance of cardiolipin in mutants. In addition, muscles and neurons were identified as key targets for future therapies because sir2 or pgc-1α overexpression in either of these tissues is sufficient to restore the exercise capacity of Drosophila tafazzin mutants.
Recommended Citation
Damschroder, Deena Jan, "Improving Mitochondrial Metabolism Restores The Exercise Capacity Of A Drosophila Model Of Barth Syndrome" (2021). Wayne State University Dissertations. 3536.
https://digitalcommons.wayne.edu/oa_dissertations/3536