Table 1.
NRF2 target proteins involved in mitochondrial biology and function
| Categories | Functions | Involved gene products |
|---|---|---|
| Nutrient Uptake/Transport | ↑ Glucose uptake | GLUT, ADIPO, ADIPOR |
| ↑ Fatty acid uptake | CD36, SLC27AI/2, ACSL, CPTI/2, FABP 3/4 | |
| ↑ Amino acid uptake | GOTI/2. GCI/2 | |
| ↑ Metabolites uptake | PDH. ACSL | |
| Intermediary Metabolism | ↑ Glycolysis | HK, PFK, PK, ME1, GSR |
| ↑ Amino acid degradation/Ketolysis | HIBCH. BCKDHA/B, BDHI, OAT | |
| ↓ Gluconeogenesis | G6PC,PEPC | |
| ↓ Lipogenesis | ACAC, ACLY, SCDI, FABP5, ELOVL | |
| Oxidative Phosphorylation | ↑ Complex I/II/III/IV/V subunits | |
| ↑ Electron transfer proteins/donors | CYCS, CYCI, CoQ, NADH, FADH2 | |
| TCA Cycle | ↑ Entry of metabolic substrates | Acetyl CoA, Malate, α-KG |
| ↑ NADH/FADH2 generation | MEI, G6PD, IDHI, ACAD | |
| ↑ Enzyme transcription | CS, ACO2, IDH3A/B, OGDH, SUCL, SDHA/B/C, MDH1/2. | |
| Lipid Metabolism | ↑ FAO substrates | FAD+/NAD+, FABP 3/4 |
| ↑ FAO enzyme transcription | ACSL, ACADL/M/S, ECHSI/ECHI, HADHA/B, ACATI | |
| ↑ Steroid hormone metabolism | AKRIBI5 | |
| Redox Homeostasis | ↓ ROS | SOD2, TRX2, TXNRD2, PRDXI/5, ALDH2/6/9/IBI, UCP3 |
| ↑ NADP/NAIY synthesis | MEI, G6PD, IDHI, PGD | |
| ↑ GSH synthesis | xCT, GG T, GST-AI/TI/PI, GS, GSR, GPXI/2/4, GCLC, GCLM | |
| ↑ GSH uptake | OGC, DIC, TTC | |
| ↑ Protein S-glutathionylation | GRX2, GST-P | |
| Quality Control | ↑ Biogenesis | PGC-Iα, NRF-I, NRF-2, T FAM, HO-I |
| ↑ Mitophagy | PINKI, PARK2, p62/SQSTRMI, LC3 | |
| ↑ Fusion/Fission | MFNI/2, DRPI | |
| ↑ Apoptosis | CYC, HSP40 | |
| ↑ Mobility | MIRO2 | |
| ↑ mtDNA repair | OGGI | |
| ↑ Calcium homeostasis | MCUI | |
| ↑ Membrane integrity | CRDI | |
| Cancer & Rapid Proliferating Cells | ↑ Pentose phosphate pathway | G6PD, PGD, MEI, TKT, TALDOI, PPAT, MTHFD2 |
| ↑ Lipid biosynthesis | ACACA, FASN, SCDI, ACLY | |
| ↑ Glutamate pathway | GLSI, GLUD |
↑, increase in function. ↓, decrease in function. ACAC, acetyl-CoA carboxylase; ACAD, acyl-CoA dehydrogenase; ACAT1, acetyl-CoA acetyltransferase, mitochondrial; ACLY, ATP-citrate lyase; ACSL, acyl-CoA synthetase long-chain family member; ACO2, aconitase 2; ADIPO, adiponectin, C1Q and collagen collagen domain containing; ADIPOR, adiponectin receptor; ALDH, aldehyde dehydrogenase; BCKDH, branched chain ketoacid dehydrogenase E1; BDH1, 3-hydroxybutyrate dehydrogenase, type 1 CoQ, coenzyme Q; CPT, carnitine O-palmitoyltransferase; CRD1, cardiolipin synthase; CS, citrate synthase; CYC1, cytochrome c1; CYCS, cytochrome c, somatic; DIC1, mitochondrial dicarboxylate transporter; DRP1, dystrophin related protein 1; ECH, enoyl Coenzyme A hydratase; ELOVL, ELOVL fatty acid elongase; FABP, fatty acid binding protein; FAO, fatty acid-β-oxidation; FASN, fatty acid synthase; FH, fumarate hydratase; G6PC, glucose-6-phosphate dehydrogenase; GC, mitochondrial glutamate carrier; GCLC, glutamate-cysteine ligase catalytic subunit; GCLM GCL modifier subunit; GGT, γ-glutamyltransferase; GLS, glutaminase; GLUD, glutamate dehydrogenase; GLUT, glucose transporter; GOT, glutamic-oxaloacetic transaminase; GPX, glutathione peroxidase; GRX2, glutaredoxin 2; GS, glutathione synthase; GSH, glutathione; GSR, glutathione reductase; GST, glutathione-S-transferase; HADH, hydroxyacyl-CoA dehydrogenase; HIBCH, 3-hydroxyisobutyryl-CoA hydrolase; HK, hexokinase; HO-1, heme oxygenase 1; HSP40, heat shock protein 40; IDH1, isocitrate dehydrogenase (NADP(+)) 1, cytosolic; KEAP1, Kelch-like ECH-associated protein 1; α-KG, α-ketoglutarate; LC3 (MAP1LC3), microtubule Associated Protein 1 Light Chain 3; MCU1, mitochondrial calcium uniporter; MDH, malate dehydrogenase; ME, malic enzyme; MFN, mitofusin; MIRO2, mitochondrial rho GTPase 2; MTHFD2, methylenetetrahydrofolate dehydrogenase (NADP+ Dependent) 2; NRF-1, nuclear respiratory factor-1; OAT, ornithine aminotransferase; OGC, oxoglutarate carrier; OGDH, oxoglutarate dehydrogenase; OGG1, 8-oxoguanine DNA glycosylase; PARK2, parkin; PDH, pyruvate dehydrogenase; PEPC, peptidase C; PFK, Phosphofructokinase; PGC-1α, peroxisome proliferative activated receptor, gamma, coactivator 1 α; PGD, phosphogluconate dehydrogenase; PINK1, PTEN-induced kinase 1; PK, pyruvate kinase; PPAT, phosphoribosyl pyrophosphate amidotransferase; PRDX, peroxiredoxin; SCD1, stearoyl-CoA desaturase; SDH, succinate dehydrogenase complex; SLC, solute carrier family; SOD2, superoxide dismutase 2; SQSTM1, sequestosome 1; SUCL, succinate-CoA ligase; TALDO1, transladolase 1; TCA, tricarboxylic acid; TFAM, transcription factor A, mitochondrial; TKT, transketolase; TRX2, thioredoxin 2; TTC, tricarboxylate carrier; TXNRD2, thioredoxin reductase 2; UCP3, uncoupling protein 3; xCT, cystine/glutamate transporter.