Nicotinamide Riboside Restores Mitochondrial Function in Rev1-Deficient Cells: Preclinical Findings

Synopsis

DNA, which carries the genetic information of all organisms, is constantly exposed to damage from both internal and external sources. If this damage—like single- or double-strand breaks—is not repaired, it can block DNA replication, causing stress for the cell and potentially halting the cell cycle. Translesion synthesis (TLS) DNA polymerases, such as Rev1, can bypass some DNA lesions, helping cells continue replicating DNA despite damage. This study found that cells and liver tissue lacking Rev1 experience replication stress and mitochondrial dysfunction. These cells also have higher PARP1 activity, lower NAD+ levels, reduced SIRT1 and PGC1α expression, and lower AMPK activity. Importantly, treatment with nicotinamide riboside (NR) restored mitochondrial function and increased the mitochondrial reserve capacity to levels seen in normal cells, suggesting that NAD+ depletion underlies the mitochondrial defects in Rev1-deficient cells and that NR can prevent these problems.

Journal

Scientific Reports