Role of METTL20 in regulating β-oxidation and heat production in mice under fasting or ketogenic conditions
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- Shimazu, Tadahiro
- Cellular Memory Laboratory, RIKEN
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- Furuse, Tamio
- Japan Mouse Clinic, RIKEN BRC
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- Balan, Shabeesh
- Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute
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- Yamada, Ikuko
- Japan Mouse Clinic, RIKEN BRC
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- Okuno, Shuzo
- Graduate School of Biostudies, Kyoto University
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- Iwanari, Hiroko
- Department of Quantitative Biology and Medicine, Research Center for Advanced Science and Technology, The University of Tokyo
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- Suzuki, Takehiro
- Biomolecular Characterization Unit, RIKEN Center for Sustainable Resource Science
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- Hamakubo, Takao
- Department of Quantitative Biology and Medicine, Research Center for Advanced Science and Technology, The University of Tokyo
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- Dohmae, Naoshi
- Biomolecular Characterization Unit, RIKEN Center for Sustainable Resource Science
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- Yoshikawa, Takeo
- Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute
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- Wakana, Shigeharu
- Japan Mouse Clinic, RIKEN BRC
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- Shinkai, Yoichi
- Cellular Memory Laboratory, RIKEN
説明
METTL20 is a seven-β-strand methyltransferase that is localised to the mitochondria and tri-methylates the electron transfer flavoprotein (ETF) β 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 β-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 β-oxidation is highly activated.
収録刊行物
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- Scientific Reports
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Scientific Reports 8 1179-, 2018-01-19
Springer Nature
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詳細情報 詳細情報について
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- CRID
- 1050001338207901056
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- NII論文ID
- 120006539598
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- ISSN
- 20452322
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- HANDLE
- 2433/235235
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- 本文言語コード
- en
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- 資料種別
- journal article
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- データソース種別
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- IRDB
- Crossref
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