Table 2.
Gene expression after complex I inhibition by MPP in LUHMES cells
| Gene | Fold change | p value | RPKM baseline | Gene name |
|---|---|---|---|---|
| Glycolysis | ||||
| GCK | 3.16 | 1E − 31 | 2 | Glucokinase |
| HK1 | 2.49 | 4E − 33 | 29 | Hexokinase 1 |
| HK2 | 3.72 | 6E − 72 | 3 | Hexokinase 2 |
| GPI | 3.25 | 3E − 48 | 13 | Glucose-6-phosphate isomerase |
| PFKM | 1.89 | 6E − 14 | 24 | Phosphofructokinase, muscle |
| ALDOA | 3.92 | 4E − 62 | 45 | Fructose-bisphosphate aldolase A |
| ALDOC | 4.23 | 5E − 75 | 11 | Fructose-bisphosphate aldolase C |
| TPI1 | 2.82 | 1E − 37 | 264 | Triosephosphate isomerase 1 |
| GAPDH | 2.93 | 3E − 36 | 642 | Glyceraldehyde-3-phosphate dehydrogenase |
| PGAM2 | 2.82 | 3E − 08 | 2 | Phosphoglycerate mutase 2 (muscle) |
| ENO1 | 2.17 | 4E − 25 | 157 | Enolase 1 |
| ENO2 | 2.38 | 5E − 35 | 30 | Enolase 2 |
| ENO3 | 5.03 | 9E − 105 | 31 | Enolase 3 |
| PKM | 1.49 | 5E − 07 | 91 | Pyruvate kinase M1/2 |
| Citric acid cycle | ||||
| CS | 3.53 | 4E − 65 | 31 | Citrate synthase |
| ACO2 | 1.95 | 3E − 17 | 33 | Aconitase 2 |
| IDH1 | 1.40 | 7E − 07 | 53 | Isocitrate dehydrogenase 1 (NADP +) |
| IDH2 | 1.93 | 9E − 17 | 23 | Isocitrate dehydrogenase 2 (NADP +) |
| IDH3B | 1.93 | 4E − 18 | 28 | Isocitrate dehydrogenase 3 (NAD +) non-catalytic subunit β |
| IDH3G | 1.67 | 1E − 08 | 13 | Isocitrate dehydrogenase 3 (NAD +) non-catalytic subunit γ |
| DLD | 0.53 | 5E − 14 | 19 | Dihydrolipoamide dehydrogenase |
| SUCLG1 | 3.14 | 4E − 47 | 18 | Succinate-CoA ligase subunit α |
| SUCLG2 | 2.01 | 1E − 08 | 2 | Succinate-CoA ligase [GDP-forming] subunit β |
| SDHA | 1.73 | 7E − 17 | 10 | Succinate dehydrogenase complex flavoprotein subunit A |
| SDHB | 1.80 | 2E − 13 | 23 | Succinate dehydrogenase complex iron sulfur subunit B |
| FH | 2.81 | 5E − 36 | 25 | Fumarate hydratase |
| MDH2 | 2.71 | 4E − 36 | 44 | Malate dehydrogenase 2, mitochondrial |
| Pentose phosphate pathway | ||||
| G6PD | 1.75 | 9E − 14 | 56 | Glucose-6-phosphate dehydrogenase |
| PGLS | 2.13 | 1E − 14 | 11 | 6-Phosphogluconolactonase |
| PGD | 3.16 | 3E − 45 | 117 | Phosphogluconate dehydrogenase |
| TKT | 8.63 | 4E − 153 | 24 | Transketolase |
| Citrate shuttle | ||||
| CS | 3.53 | 4E − 65 | 31 | Citrate synthase |
| SLC25A1 | 4.11 | 9E − 78 | 16 | Solute carrier family 25 member 1 |
| ACLY | 1.47 | 2E − 09 | 146 | ATP citrate lyase |
| MDH2 | 2.72 | 4E − 36 | 44 | Malate dehydrogenase 2, mitochondrial |
| ME1 | 7.78 | 2E − 97 | 1 | Malic enzyme 1, cytosolic |
| ME2 | 1.79 | 3E − 18 | 7 | Malic enzyme 2, mitochondrial |
| MPC2 | 2.89 | 4E − 31 | 7 | Mitochondrial pyruvate carrier 2 |
| Fatty acid synthesis | ||||
| ACACA | 2.77 | 1E − 53 | 11 | Acetyl-CoA carboxylase α |
| ACSL1 | 0.44 | 3E − 26 | 12 | Long-chain-fatty-acid—CoA ligase 1 |
| ACSL3 | 2.07 | 8E − 11 | 18 | Long-chain-fatty-acid—CoA ligase 3 |
| ACSL4 | 1.92 | 7E − 11 | 12 | Long-chain-fatty-acid—CoA ligase 4 |
| ELOVL1 | 2.10 | 2E − 18 | 5 | ELOVL fatty acid elongase 1 |
| ELOVL5 | 2.69 | 4E − 57 | 35 | ELOVL fatty acid elongase 5 |
| ELOVL6 | 1.69 | 8E − 08 | 11 | ELOVL fatty acid elongase 6 |
| HACD2 | 0.46 | 2E − 14 | 3 | Very-long-chain 3-hydroxyacyl-CoA dehydratase 2 |
| TECR | 1.68 | 3E − 11 | 14 | Trans-2,3-enoyl-CoA reductase |
| SCD | 7.78 | 8E − 255 | 160 | Stearoyl-CoA desaturase |
| SCD5 | 1.73 | 1E − 12 | 6 | Stearoyl-CoA desaturase 5 |
| Carnitine shuttle (n.a.) | ||||
| Fatty acid oxidation | ||||
| ACADM | 0.40 | 1E − 18 | 13 | Acyl-CoA dehydrogenase, medium chain |
| ACADVL | 2.16 | 9E − 23 | 20 | Acyl-CoA dehydrogenase very long chain |
| ACAD9 | 0.50 | 1E − 13 | 8 | Acyl-CoA dehydrogenase family member 9 |
| HADH | 4.14 | 1E − 67 | 6 | Hydroxyacyl-CoA dehydrogenase |
| HADHA | 1.69 | 9E − 15 | 53 | Trifunctional enzyme subunit α |
| HADHB | 1.99 | 7E − 23 | 20 | Trifunctional enzyme subunit β |
Sampling of all significantly induced or repressed genes (p < 10−6; n = 3) with robust baseline expression (RPKM > 1) for the following metabolic pathways: glycolysis, citric acid cycle, pentose phosphate pathway, citrate shuttle, fatty acid synthesis, carnitine shuttle, and fatty acid oxidation. A complete list of genes irrespective of their p value is provided in Suppl. Tab. 1, including a sampling of all detected NADPH-generating enzymes. n.a., not applicable (no significant changes occurred)