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. Author manuscript; available in PMC: 2021 Jul 5.
Published in final edited form as: Sci Signal. 2021 Jan 5;14(664):eabc4436. doi: 10.1126/scisignal.abc4436

Figure 3. HLRCC FH−/− tumors exhibited down-regulation of mitochondrial encoded mRNAs, which resulted from decreased mtDNA copy number.

Figure 3.

(A) RNAseq pathway analysis of nuclear-encoded and mtDNA-encoded genes in HLRCC tumor (T; n=5 patient samples) and metastases (M; n=16 patient samples) and paired renal cortex samples (n=5 patient samples), organized according to Krebs cycle and electron transport chain complex. (B) qPCR measurement of the mRNA expression of the NRF2 transcriptional target G6PD showed upregulation in FH−/− primary tumors (prim. tumors) and metastases (mets) versus FH+/− renal cortex (P=0.0010, cortex vs tumors, Wilcoxon Two-Sample Test). (C) qPCR revealed no significant change in mRNA expression of the nuclear-encoded NDUFS1 in FH+/− renal cortex versus FH−/− primary tumors and metastases (P=0.2522, cortex vs tumors). (D) qPCR measurement demonstrated decreased mRNA expression of MT-ND1 in FH−/− primary tumors and metastases versus FH+/− renal cortex (P=0.0020, cortex vs tumors). For (B) to (D), n=6 independent primary tumor samples, n=16 metastatic tumor samples obtained from seven patients, and n=5 independent FH+/− renal cortex samples. (E) qPCR measurement of mtDNA copy number relative to nuclear DNA content demonstrated significant (P=0.0012, cortex vs tumors) decrease in mtDNA content in FH−/− primary tumors (n=6 patient samples) and FH−/− metastases (n=16 metastatic tumor samples obtained from 14 patients) versus FH+/− renal cortex (n=7 patient samples).