| First Author | Shimazu T | Year | 2018 |
| Journal | Sci Rep | Volume | 8 |
| Issue | 1 | Pages | 1179 |
| PubMed ID | 29352221 | Mgi Jnum | J:260200 |
| Mgi Id | MGI:6148369 | Doi | 10.1038/s41598-018-19615-4 |
| Citation | Shimazu T, et al. (2018) Role of METTL20 in regulating beta-oxidation and heat production in mice under fasting or ketogenic conditions. Sci Rep 8(1):1179 |
| abstractText | METTL20 is a seven-beta-strand methyltransferase that is localised to the mitochondria and tri-methylates the electron transfer flavoprotein (ETF) beta subunit (ETFB) at lysines 200 and 203. It has been shown that METTL20 decreases the ability of ETF to extract electrons from medium-chain acyl-coenzyme A (CoA) dehydrogenase (MCAD) and glutaryl-CoA dehydrogenase in vitro. METTL20-mediated methylation of ETFB influences the oxygen consumption rate in permeabilised mitochondria, suggesting that METTL20-mediated ETFB methylation may also play a regulatory role in mitochondrial metabolism. In this study, we generated Mettl20 knockout (KO) mice to uncover the in vivo functions of METTL20. The KO mice were viable, and a loss of ETFB methylation was confirmed. In vitro enzymatic assays revealed that mitochondrial ETF activity was higher in the KO mice than in wild-type mice, suggesting that the KO mice had higher beta-oxidation capacity. Calorimetric analysis showed that the KO mice fed a ketogenic diet had higher oxygen consumption and heat production. A subsequent cold tolerance test conducted after 24 h of fasting indicated that the KO mice had a better ability to maintain their body temperature in cold environments. Thus, METTL20 regulates ETF activity and heat production through lysine methylation when beta-oxidation is highly activated. |
