Consistent with this, AP-1 transcriptional activity was increased after SIRT3 deletion (Fig. 2f), and this was correlated with the enhanced expression of the AP-1 target gene ATF4 (activating transcription factor 4; Supplementary Fig. S1e), a profibrotic transcription factor that controls the synthesis of type I collagen and other fibrosis-related proteins.19 In fact, SIRT3 knockout mice spontaneously developed myocardial fibrosis, since the collagen content in the heart was higher in knockout mice than in WT mice (Fig. 2g). The gene discussed is JUN; the disease is Myocardial fibrosis.