Synergism and Antagonism of Two Distinct, but Confused, Nrf1 Factors in Integral Regulation of the Nuclear-to-Mitochondrial Respiratory and Antioxidant Transcription Networks

Figure 9

A hierarchical interaction network integrated with those relevant genes involved in the nuclear-to-mitochondrial communication. (a, b) Two interaction subnetworks with Pitx2- and Pitx3-regulated genes. (c–e) A core subnetwork of redox-relevant genes regulated by Nfe2l1 and/or Nfe2l2, together with Nfe2l1- and/or Nfe2l2-interactors in additional two extended subnetworks. (f–j) Five subnetworks are monitored by α-Pal^NRF1, GABPα^NRF2, TFAM, TFB1M, and/or TFB2M, which are key players as the nuclear controls of mitochondrial biogenesis and function. (k–m) Differentially expressed genes (DEGs) are contributed by the Nfe2l1α-inducible expression. Their FPKM values () were obtained from RNA-sequencing of Nfe2l1α-induced cells versus WT cells. Such DEGs were also shown by two distinct heat maps, as scaled in different ways. (n–p) 14 of DEGs are regulated by Nfe2l2-inducible expression, which are also shown in two distinct fashions as described above.