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Role of METTL20 in regulating β-oxidation and heat production in mice under fasting or ketogenic conditions

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...

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Autores principales: Shimazu, Tadahiro, Furuse, Tamio, Balan, Shabeesh, Yamada, Ikuko, Okuno, Shuzo, Iwanari, Hiroko, Suzuki, Takehiro, Hamakubo, Takao, Dohmae, Naoshi, Yoshikawa, Takeo, Wakana, Shigeharu, Shinkai, Yoichi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5775328/
https://www.ncbi.nlm.nih.gov/pubmed/29352221
http://dx.doi.org/10.1038/s41598-018-19615-4
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author Shimazu, Tadahiro
Furuse, Tamio
Balan, Shabeesh
Yamada, Ikuko
Okuno, Shuzo
Iwanari, Hiroko
Suzuki, Takehiro
Hamakubo, Takao
Dohmae, Naoshi
Yoshikawa, Takeo
Wakana, Shigeharu
Shinkai, Yoichi
author_facet Shimazu, Tadahiro
Furuse, Tamio
Balan, Shabeesh
Yamada, Ikuko
Okuno, Shuzo
Iwanari, Hiroko
Suzuki, Takehiro
Hamakubo, Takao
Dohmae, Naoshi
Yoshikawa, Takeo
Wakana, Shigeharu
Shinkai, Yoichi
author_sort Shimazu, Tadahiro
collection PubMed
description 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.
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spelling pubmed-57753282018-01-26 Role of METTL20 in regulating β-oxidation and heat production in mice under fasting or ketogenic conditions Shimazu, Tadahiro Furuse, Tamio Balan, Shabeesh Yamada, Ikuko Okuno, Shuzo Iwanari, Hiroko Suzuki, Takehiro Hamakubo, Takao Dohmae, Naoshi Yoshikawa, Takeo Wakana, Shigeharu Shinkai, Yoichi Sci Rep Article 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. Nature Publishing Group UK 2018-01-19 /pmc/articles/PMC5775328/ /pubmed/29352221 http://dx.doi.org/10.1038/s41598-018-19615-4 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Shimazu, Tadahiro
Furuse, Tamio
Balan, Shabeesh
Yamada, Ikuko
Okuno, Shuzo
Iwanari, Hiroko
Suzuki, Takehiro
Hamakubo, Takao
Dohmae, Naoshi
Yoshikawa, Takeo
Wakana, Shigeharu
Shinkai, Yoichi
Role of METTL20 in regulating β-oxidation and heat production in mice under fasting or ketogenic conditions
title Role of METTL20 in regulating β-oxidation and heat production in mice under fasting or ketogenic conditions
title_full Role of METTL20 in regulating β-oxidation and heat production in mice under fasting or ketogenic conditions
title_fullStr Role of METTL20 in regulating β-oxidation and heat production in mice under fasting or ketogenic conditions
title_full_unstemmed Role of METTL20 in regulating β-oxidation and heat production in mice under fasting or ketogenic conditions
title_short Role of METTL20 in regulating β-oxidation and heat production in mice under fasting or ketogenic conditions
title_sort role of mettl20 in regulating β-oxidation and heat production in mice under fasting or ketogenic conditions
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5775328/
https://www.ncbi.nlm.nih.gov/pubmed/29352221
http://dx.doi.org/10.1038/s41598-018-19615-4
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