Figure 10.

Schematic of the transcriptional regulation of mitochondrial and metabolic genes by GLIS3 likely in coordination with HNF1B and NRF1. (A) GLIS3 activates the transcription of several mitochondrial and metabolic genes during postnatal kidney development in coordination with HNF1B and NRF1. However, some genes are likely regulated indirectly via the increased expression of other key regulators of transcription (e.g., Tfam, Tfb1/2m, Ppargc1a/b, Polrmt) that themselves are GLIS3 transcriptional targets. Together this enhances mitochondrial-related gene expression and OXPHOS. (B) Loss of GLIS3 function suppresses the normal induction of these mitochondrial-related genes leading to a decrease in mtDNA and OXPHOS compared to WT, and an increase in aerobic glycolysis and lactate production.