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. Overall design: RNA sequencing in SV40T immortalized SIRT3 WT (triplicates) and SIRT3 KO MEF (duplicates) lines under normal conditions.

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Gonzalez Herrera KN, Zaganjor E, Ishikawa Y, Spinelli JB, Yoon H, Lin JR, Satterstrom FK, Ringel A, Mulei S, Souza A, Gorham JM, Benson CC, Seidman JG, Sorger PK, Clish CB, Haigis MC