SIRT4 and neoplasm: SIRT4 is a known repressor of GDH and is located in the mitochondria.23, 25, 26, 29 Several recent studies demonstrated that SIRT4 is required to inhibit glutamine-dependent metabolism in response to DNA-damage stress and prohibit the tumor growth in different tissues.23, 25, 26, 29 Interestingly, in previous gene expression microarray data, SIRT4 mRNA showed significant upregulation upon CtBP knockdown in MCF-7 cells.19 In addition, a significant binding peak was identified at SIRT4 gene promoter in CtBP genome-wide-binding profile analysis (Supplementary Figure 3A).