Mitochondrial Methionyl-tRNA Formyltransferase Deficiency Alleviates Metaflammation by Modulating Mitochondrial Activity in Mice
Various studies have revealed the association of metabolic diseases with inflammation. Mitochondria are key organelles involved in metabolic regulation and important drivers of inflammation. However, it is uncertain whether the inhibition of mitochondrial protein translation results in the developme...
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MDPI AG
2023-03-01
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| Series: | International Journal of Molecular Sciences |
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| author | Xiaoxiao Sun Suyuan Liu Jiangxue Cai Miaoxin Yang Chenxuan Li Meiling Tan Bin He |
| author_facet | Xiaoxiao Sun Suyuan Liu Jiangxue Cai Miaoxin Yang Chenxuan Li Meiling Tan Bin He |
| author_sort | Xiaoxiao Sun |
| collection | DOAJ |
| description | Various studies have revealed the association of metabolic diseases with inflammation. Mitochondria are key organelles involved in metabolic regulation and important drivers of inflammation. However, it is uncertain whether the inhibition of mitochondrial protein translation results in the development of metabolic diseases, such that the metabolic benefits related to the inhibition of mitochondrial activity remain unclear. Mitochondrial methionyl-tRNA formyltransferase (Mtfmt) functions in the early stages of mitochondrial translation. In this study, we reveal that feeding with a high-fat diet led to the upregulation of Mtfmt in the livers of mice and that a negative correlation existed between hepatic <i>Mtfmt</i> gene expression and fasting blood glucose levels. A knockout mouse model of <i>Mtfmt</i> was generated to explore its possible role in metabolic diseases and its underlying molecular mechanisms. Homozygous knockout mice experienced embryonic lethality, but heterozygous knockout mice showed a global reduction in Mtfmt expression and activity. Moreover, heterozygous mice showed increased glucose tolerance and reduced inflammation, which effects were induced by the high-fat diet. The cellular assays showed that <i>Mtfmt</i> deficiency reduced mitochondrial activity and the production of mitochondrial reactive oxygen species and blunted nuclear factor-κB activation, which, in turn, downregulated inflammation in macrophages. The results of this study indicate that targeting <i>Mtfmt</i>-mediated mitochondrial protein translation to regulate inflammation might provide a potential therapeutic strategy for metabolic diseases. |
| first_indexed | 2024-03-11T06:24:25Z |
| format | Article |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T06:24:25Z |
| publishDate | 2023-03-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-c891e91f00bd496e81e06a03c62679fa2023-11-17T11:42:06ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-03-01246599910.3390/ijms24065999Mitochondrial Methionyl-tRNA Formyltransferase Deficiency Alleviates Metaflammation by Modulating Mitochondrial Activity in MiceXiaoxiao Sun0Suyuan Liu1Jiangxue Cai2Miaoxin Yang3Chenxuan Li4Meiling Tan5Bin He6Key Laboratory of Animal Physiology & Biochemistry, Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, ChinaKey Laboratory of Animal Physiology & Biochemistry, Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, ChinaKey Laboratory of Animal Physiology & Biochemistry, Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, ChinaKey Laboratory of Animal Physiology & Biochemistry, Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, ChinaKey Laboratory of Animal Physiology & Biochemistry, Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, ChinaKey Laboratory of Animal Physiology & Biochemistry, Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, ChinaKey Laboratory of Animal Physiology & Biochemistry, Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, ChinaVarious studies have revealed the association of metabolic diseases with inflammation. Mitochondria are key organelles involved in metabolic regulation and important drivers of inflammation. However, it is uncertain whether the inhibition of mitochondrial protein translation results in the development of metabolic diseases, such that the metabolic benefits related to the inhibition of mitochondrial activity remain unclear. Mitochondrial methionyl-tRNA formyltransferase (Mtfmt) functions in the early stages of mitochondrial translation. In this study, we reveal that feeding with a high-fat diet led to the upregulation of Mtfmt in the livers of mice and that a negative correlation existed between hepatic <i>Mtfmt</i> gene expression and fasting blood glucose levels. A knockout mouse model of <i>Mtfmt</i> was generated to explore its possible role in metabolic diseases and its underlying molecular mechanisms. Homozygous knockout mice experienced embryonic lethality, but heterozygous knockout mice showed a global reduction in Mtfmt expression and activity. Moreover, heterozygous mice showed increased glucose tolerance and reduced inflammation, which effects were induced by the high-fat diet. The cellular assays showed that <i>Mtfmt</i> deficiency reduced mitochondrial activity and the production of mitochondrial reactive oxygen species and blunted nuclear factor-κB activation, which, in turn, downregulated inflammation in macrophages. The results of this study indicate that targeting <i>Mtfmt</i>-mediated mitochondrial protein translation to regulate inflammation might provide a potential therapeutic strategy for metabolic diseases.https://www.mdpi.com/1422-0067/24/6/5999Mitochondrial methionyl-tRNA formyltranse (Mtfmt)mitochondriamitochondrial reactive oxygen species (mROS)metaflammationmetabolic disorder |
| spellingShingle | Xiaoxiao Sun Suyuan Liu Jiangxue Cai Miaoxin Yang Chenxuan Li Meiling Tan Bin He Mitochondrial Methionyl-tRNA Formyltransferase Deficiency Alleviates Metaflammation by Modulating Mitochondrial Activity in Mice International Journal of Molecular Sciences Mitochondrial methionyl-tRNA formyltranse (Mtfmt) mitochondria mitochondrial reactive oxygen species (mROS) metaflammation metabolic disorder |
| title | Mitochondrial Methionyl-tRNA Formyltransferase Deficiency Alleviates Metaflammation by Modulating Mitochondrial Activity in Mice |
| title_full | Mitochondrial Methionyl-tRNA Formyltransferase Deficiency Alleviates Metaflammation by Modulating Mitochondrial Activity in Mice |
| title_fullStr | Mitochondrial Methionyl-tRNA Formyltransferase Deficiency Alleviates Metaflammation by Modulating Mitochondrial Activity in Mice |
| title_full_unstemmed | Mitochondrial Methionyl-tRNA Formyltransferase Deficiency Alleviates Metaflammation by Modulating Mitochondrial Activity in Mice |
| title_short | Mitochondrial Methionyl-tRNA Formyltransferase Deficiency Alleviates Metaflammation by Modulating Mitochondrial Activity in Mice |
| title_sort | mitochondrial methionyl trna formyltransferase deficiency alleviates metaflammation by modulating mitochondrial activity in mice |
| topic | Mitochondrial methionyl-tRNA formyltranse (Mtfmt) mitochondria mitochondrial reactive oxygen species (mROS) metaflammation metabolic disorder |
| url | https://www.mdpi.com/1422-0067/24/6/5999 |
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