Small molecule screen identifies de novo nucleotide synthesis as a vulnerability of cells lacking SIRT3

Sirtuin 3 (SIRT3) is an NAD+-dependent deacetylase downregulated in aging and age-associated diseases such as cancer and neurodegeneration, and high fat diet (HFD)-induced metabolic disorders. Thus, we performed a small molecule screen and identified an unexpected metabolic vulnerability associated with SIRT3 loss. RNA sequencing in SV40T immortalized SIRT3 WT (triplicates) and SIRT3 KO MEF (duplicates) lines under normal conditions.