Figure 3.

ERRγ is an essential regulator of the mitochondrial OXPHOS program in pancreatic acinar cells. (A-B) Gene ontology (GO) (A) and gene set enrichment analysis (GSEA) (B) of top rank enriched cellular components between ERRγ cKO primary acini and ERRγ adenovirus transduced (ERRγ OE) primary acini, compared to respective controls (CON). (C) Heatmap for differential gene expression in ERRγ cKO primary acini and ERRγ OE primary acini, compared to respective controls. (D-G) Pancreatic RNA, DNA, and protein were extracted from control and ERRγ cKO mice 7 d after the final TAM injection. (D) Mitochondrial DNA content was quantified by ND1 (mtDNA) / HK2 (nDNA) ratio. (E) Western blot for OXPHOS complex proteins in pancreas from control and ERRγ cKO mice. α-tubulin, loading control. (F) Quantitation of protein levels from (E) normalized to α-Tubulin expression. (G) Relative gene expression of PGC1α and PGC1β. (H) Scheme of experiments. Primary acini from C57BL/6J mice were treated with vehicle or GSK5182 (10 μM) for 48 h. (I-M) Extracellular flux analysis measurements for (I) oxygen consumption rate, (J) basal respiration, (K) maximal respiration, (L) ATP production and (M) spare capacity. CON, control; cKO, ERRγ cKO. All data are presented as mean ± SEM. ** p < 0.01, *** p < 0.005 by student’s t-test.