Restoring NAD+ with Nicotinamide Riboside Improves Metabolism and Autophagy in DNA Repair Deficiency: Preclinical Findings
Synopsis
Loss of Rev1, a DNA repair protein, causes replication stress, mitochondrial dysfunction, and metabolic imbalance. This study found that mouse embryonic fibroblasts lacking Rev1 had altered lipid and nucleotide metabolism, reduced autophagy, and abnormal mitochondrial morphology. Supplementing with nicotinamide riboside (NR) restored NAD+ levels, improved autophagy, and partially corrected mitochondrial defects. However, NR did not rescue oxidative stress sensitivity in Rev1-deficient nematodes. These findings demonstrate that NR supplementation can reverse key metabolic and cellular defects caused by Rev1 deficiency in mammalian cells.
Journal
Heliyon