Stimulating the sir2-spargel axis rescues exercise capacity and mitochondrial respiration in a Drosophila model of Barth syndrome.

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 can rescue exercise tolerance and mitochondrial respiration in a Drosophila Tafazzin mutant and that the beneficial effects are dependent on sir2 and spargel. Overexpressing spargel increa

SUBMITTER: Damschroder D 

PROVIDER: S-EPMC9558626 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature