NAD supplementation improves mitochondrial performance of cardiolipin mutants.

Abstract

Cardiolipin (CL) deficiency causes mitochondrial dysfunction and aberrant metabolism that are associated in humans with the severe disease Barth syndrome (BTHS). Several metabolic abnormalities are observed in BTHS patients and model systems, including decreased oxidative phosphorylation, reduced tricarboxylic acid (TCA) cycle flux, and accumulated lactate and D-β-hydroxybutyrate, which strongly suggests that nicotinamide adenine dinucleotide (NAD) redox metabolism may be altered in CL-deficient cells. In this study, we identified abnormal NAD+ metabolism in multiple BTHS model systems and demonstrate that supplementation of NAD+ precursors such as nicotinamide mononucleotide (NMN) improves mitochondrial function. Improved mitochondrial function in the Drosophila model was associated with restored exercise endurance, which suggests a potential therapeutic benefit of NAD+ precursor supplementation in the management of BTHS patients.

• Authors: Jiajia Ji, Deena Damschroder, Denise Bessert, Pablo Lazcano, Robert Wessells, Christian A Reynolds, Miriam L Greenberg
• Journal: Biochimica et biophysica acta. Molecular and cell biology of lipids (Biochim Biophys Acta Mol Cell Biol Lipids) Vol. 1867 Issue 4 Pg. 159094 (04 2022) ISSN: 1879-2618 [Electronic] Netherlands
• PMID: 35051613 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 Elsevier B.V. All rights reserved.

Chemical References

• Cardiolipins
• NAD
• Nicotinamide Mononucleotide

Topics

• Barth Syndrome (metabolism)
• Cardiolipins (metabolism)
• Dietary Supplements
• Humans
• Mitochondria (metabolism)
• NAD (metabolism)
• Nicotinamide Mononucleotide (metabolism)