Table 2 |.
Effects of common cell metabolism-perturbing agents on subcellular lactate metabolism
| Pathway | Agent | Mechanism(s) of action | Stock solution | Final solution | Cytosolic changes | Nuclear changes | Mitochondrial changes | Extracellular changes |
|---|---|---|---|---|---|---|---|---|
| Glycolysis | 3-BrPA39 | HK II | 100 mM in HBSS-G | 500 μM | Free [lactate] decrease | Free [lactate] decrease | Free [lactate] decrease | Free [lactate] decrease |
| 2-DG | HK II | 500 mM in HBSS-G | 50 mM | Free [lactate] decrease | Free [lactate] decrease | Free [lactate] decrease | Free [lactate] decrease | |
| Oxamate39 | LDH | 400 mM in HBSS-G | 10 mM | Free [lactate] decrease | Free [lactate] decrease | Free [lactate] decrease | Free [lactate] decrease | |
| IAA | GAPDH | 10 mM in HBSS-G | 500 μM | Free [lactate] decrease | Free [lactate] decrease | Free [lactate] decrease | Free [lactate] decrease | |
| Oxalate | PK | 5 mM in HBSS-G | 500 μM | Free [lactate] decrease | Free [lactate] decrease | Free [lactate] decrease | Free [lactate] decrease | |
| UK5099 | MPC | 10 mM in DMSO | 5–10 μM | Free [lactate] increase | Free [lactate] increase | Free [lactate] increase | Free [lactate] increase | |
| TCA | Devimistat | PDH/aKGDH | 100 mM in DMSO | 100 μM | Free [lactate] increase | Free [lactate] increase | Free [lactate] decrease | Free [lactate] increase |
| ETC | Rotenone39 | Complex I | 30 mM in DMSO | 10 μM | Free [lactate] increase | Free [lactate] increase | Free [lactate] increase | Free [lactate] increase |
| Oligomycin A39 | Complex V | 5 mM in DMSO | 5 μM | Free [lactate] increase | Free [lactate] increase | Free [lactate] increase | Free [lactate] increase | |
| pH Regulation | AZD-3965 (ref. 39) | MCT1 | 10 mM in DMSO | 2 μM | Free [lactate] increase | Free [lactate] increase | Free [lactate] increase | Free [lactate] decrease |
| AR-C155858 (ref. 39) | MCT1/2 | 10 mM in DMSO | 2 μM | Free [lactate] increase | Free [lactate] increase | Free [lactate] increase | Free [lactate] decrease | |
| Fatty acid metabolism | SB-204990 (ref. 39) | ACLY | 30 mM in DMSO | 50 μM | Free [lactate] increase | Free [lactate] increase | Free [lactate] decrease | Free [lactate] increase |
| BMS-303141 (ref. 39) | ACLY | 30 mM in DMSO | 10 μM | Free [lactate] increase | Free [lactate] increase | Free [lactate] decrease | Free [lactate] increase | |
| Perhexiline maleate | CPT1 | 30 mM in DMSO | 100 μM | Free [lactate] increase | Free [lactate] increase | Free [lactate] increase | Free [lactate] increase | |
| Etomoxir | CPT1 | 30 mM in DMSO | 100 μM | Free [lactate] increase | Free [lactate] increase | Free [lactate] increase | Free [lactate] increase | |
| JZL195 | MAGL | 30 mM in DMSO | 30 μM | Free [lactate] increase | Free [lactate] increase | Free [lactate] increase | Free [lactate] increase | |
| KML29 | MAGL | 15 mM in DMSO | 100 μM | Free [lactate] increase | Free [lactate] increase | Free [lactate] increase | Free [lactate] increase | |
| mTOR | Rapamycin39 | mTOR | 10 mM in DMSO | 100 μM | Free [lactate] increase | Free [lactate] increase | Free [lactate] increase | Free [lactate] increase |
| Metabolites | Octyl-(R)-2-HG39 | ATP synthase/mTOR | 100 mM in DMSO | 500 μM | Free [lactate] increase | Free [lactate] increase | Free [lactate] increase | Free [lactate] increase |
| Octyl-(S)-2-HG39 | ATP synthase/mTOR | 100 mM in DMSO | 500 μM | Free [lactate] increase | Free [lactate] increase | Free [lactate] increase | Free [lactate] increase | |
| Ca2+ Regulation | Ionomycin39 | Calcium ionophore | 10 mM in DMSO | 2 μM | Free [lactate] increase | Free [lactate] increase | Free [lactate] decrease | Free [lactate] increase |
| Medical/health Drug | CoQ39 | Essential Cofactor of ETC | 10 mM in ethanol | 100 μM | Free [lactate] increase | Free [lactate] increase | Free [lactate] increase | Free [lactate] increase |
| MitoQ39 | Mitochondri-targeted antioxidant | 10 mM in DMSO | 10 μM | Free [lactate] increase | Free [lactate] increase | Free [lactate] increase | Free [lactate] increase | |
| Troglitazone39 | Antidiabetes medicine | 100 mM in DMSO | 100 μM | Free [lactate] increase | Free [lactate] increase | Free [lactate] decrease | Free [lactate] decrease |
Bold indicates an increase in the concentration of free Lactate ('free [Lactate]'). 3-BrPA, 3-bromopyruvic acid; HK II, hexokinase II; IAA, iodoacetamide; GAPDH, gLyceraLdehyde-3- phosphate dehydrogenase; PK, pyruvate kinase; MPC, mitochondrial pyruvate carrier; TCA, tricarboxylic acid; ETC, electron transport chain; PDH, pyruvate dehydrogenase; α-KGDH, α-ketoglutarate dehydrogenase; ATMA, antimycin A; MCT1/2, monocarboxylate transporter 1/2; ACLY, ATP citrate lyase; CPT1, carnitine palmitoyltransferase 1; MAGL, monoacylglycerol lipase; mTOR, mammalian target of rapamycin; 2-HG, 2-hydroxyglutarate; CoQ, Coenzyme Q10; MitoQ, Mitoquinone.