Fig. 3: Enhanced OXPHOS activity in hepatocytes with Zhx2 deficiency during damaged liver repair. | Nature Communications

Fig. 3: Enhanced OXPHOS activity in hepatocytes with Zhx2 deficiency during damaged liver repair.

From: ZHX2 emerges as a negative regulator of mitochondrial oxidative phosphorylation during acute liver injury

Fig. 3

a–c RNA-seq (a), quantitative proteomic analysis (b) and energy metabolomics (c) were performed with liver tissues from Zhx2-KOhep and Zhx2-WT mice at 48 h after 2/3 PHx. a GSEA was used to analyze the genes with differential mRNA levels. Data were analyzed using Kolmogorov–Smirnov test. b Percentage of per metabolic category among differential metabolic proteins was shown on the pie-chart. c Pathway analysis with MetaboAnalyst (www.metaboanalyst.ca/). Data were analyzed using Kolmogorov–Smirnov test (a), hypergeometric test (c). d The metabolites of ATP and ADP were determined by energy metabolic analysis in Zhx2-KOhep and Zhx2-WT mice liver samples. Data are presented as mean ± s.e.m. (two-tailed Student’s t-test. n = 3 mice per group). e The copy number of mtDNA was determined in hepatocytes of Zhx2-KOhep and Zhx2-WT mice at 48 h after 2/3 PHx by qPCR. Data are presented as mean ± s.e.m. (two-tailed Student’s t-test. n = 4 mice per group). f Ultrastructure of mitochondria in hepatocytes from Zhx2-KOhep and Zhx2-WT mice were analyzed at 48 h after 2/3 PHx by using transmission electron microscopy (TEM). The representative images are shown on the left panel and one mitochondrial was selected to zoom in. The quantitative data of mitochondrial volume density is shown on the right panel. Scale bar: 1 μm. Representative data are presented as mean ± sd (two-tailed Student’s t-test. n = 9 cells). g–i Mitochondrial functional status, including mitochondrial membrane potential (JC-1 aggregates) (g), extracellular O2 consumption (h), and Oxygen consumption (i) in hepatocytes from Zhx2-KOhep and Zhx2-WT mice 48 h after 2/3 PHx were accessed by the assay kits according to the manufacture protocols. Data are presented as mean ± s.e.m. (g and h: two-tailed Student’s t-test. n = 3 mice; i: two-way ANOVA with Bonferroni’s test. n = 4 mice). j ATP levels and ATP/AMP ratio were accessed in hepatocytes from Zhx2-KOhep and Zhx2-WT mice by the assay kits according to the manufacture protocols. Data are presented as mean ± s.e.m. (two-tailed Student’s t-test. n = 3 mice).

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