Fig 2: Inosine monophosphate treatment promotes mitochondrial transcription.a RT–QPCR analysis of the mRNA expression of NRF1 and mtTFA in lineage−/low cells after treated with IMP for 24 h, n = 6. b–e Western blot analysis expression level of NRF1, mtTFA and PFAS in IMP-treated cells for 24 or 72 h compared with controls, n = 15–27. Data are presented as the means ± SEM. f–h ADSS, ATPase and IMPDH2 activity in lineage−/low cells which were stimulated with IMP for 0, 4, and 8 h, n = 6. i ATP and GTP production in lineage−/low cells after 24 and 72 h of IMP treatment, n = 6. j, k Oxygen consumption rate analysis of the Lineage−/low cells which were exposed to PBS or 15 mM IMP for 6 h, n = 6. One-way ANOVA with Dunnett was used to compare groups against control. IMP Inosine-5′-monophosphate, ADSS adenylosuccinate synthetase, IMPDH2 Inosine-5′-monophosphate dehydrogenase 2, ATP Adenosine triphosphate, GTP guanosine triphosphate, NRF1 nuclear respiratory factor 1, PFAS phosphoribosylformylglycinamidine synthase.

Fig 3: CAT improves OGD/R-induced neuronal injury and excessive autophagy via the NRF1/KAT2A/METTL3 axis. A the protein expression of NRF1, KAT2A, METTL3, and Beclin-1 in RN-c cells was measured by western blotting. B RN-c cell viability was measured by CCK-8 assay. C LDH release was evaluated using the corresponding kit. D RN-c cell apoptosis was evaluated by flow cytometry. E The number of autophagosomes in RN-c cells was observed through TEM. F the expression of LC3II/I and p62 was evaluated by western blotting. G the representative images of immunofluorescent staining of LC3. Cell experiments were repeated three times. *P < 0.05, compared with the OGD/R + CAT + sh-NC + oe-NC group; #P < 0.05, compared with the OGD/R + CAT + sh-NRF1 + oe-NC group

Fig 4: Expression of sirt1, PGC-1α, Nrf1, TFAM, Mfn2, and Drp1 in ischemic myocardial tissue. (#p < 0.05, ##p < 0.01, ###p < 0.001 vs. control group; *p < 0.05, **p < 0.01, ***p < 0.001 vs. I/R group).

Fig 5: Kidney protein expression levels of NRF1, UCP1, OPA1, and FIS1. Protein expression levels of NRF1 (A), UCP1 (B), OPA1 (C), and FIS1 (D) were measured in kidneys isolated from 5‐month‐old (young) and 18‐month‐old (old) ERα−/−, AF2°, and C451A mice, and their corresponding WT littermates, treated with or without angiotensin II (Ang II). Values are presented as mean±SEM (n=8 mice per group). Western blots are shown in Figure S3. NS: ERα−/−, young vs old, AngII vs control and WT vs KO (ERα−/−, AF2°, or C451A); ordinary 2‐way ANOVA and Bonferroni multiple comparisons test. *P<0.05; **P<0.01: ERα−/−, WT vs KO; Mann‐Whitney test. KO indicates knockout; NS, nonsignificant; WT, wild type.