Nicotinamide Riboside Improves Mitochondrial Function in Mutant Human Cells: Preclinical Findings

Synopsis

Mitochondrial disorders are severe genetic conditions that disrupt energy production, and currently, no effective treatments exist. This study explored whether boosting NAD+, a vital molecule for cellular energy and mitochondrial health, could help human cells with mitochondrial defects. Researchers tested two strategies: supplementing with nicotinamide riboside (NR), a vitamin B3-derived NAD+ precursor, and inhibiting PARP-1, an enzyme that consumes NAD+. In human cells with a defective mitochondrial complex I gene (NDUFS1), both NR and PARP-1 inhibitors improved mitochondrial function and energy balance. NR increased NAD+ levels, while PARP-1 inhibitors enhanced expression of genes that regulate mitochondrial DNA and repair. Despite acting through different molecular pathways, both treatments restored mitochondrial membrane potential and boosted energy production. These findings provide the first evidence that NR supplementation and PARP-1 inhibition can independently enhance mitochondrial performance in human cells, suggesting potential therapeutic strategies for mitochondrial diseases.

Journal

Molecular Pharmacology