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| Auteurs principaux: | , , , , , , |
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| Format: | Artículo científico |
| Langue: | en |
| Publié: |
Cell death & disease
2025
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| Sujets: | |
| Accès en ligne: | https://pubmed.ncbi.nlm.nih.gov/40610445/ |
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| _version_ | 1868266181685673984 |
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| author | Sun, Xiaoya Tan, Qinmei Yang, Yue Wei, Jia Zhou, Xiaodie Gao, Shanshan Yang, Fei |
| author_facet | Sun, Xiaoya Tan, Qinmei Yang, Yue Wei, Jia Zhou, Xiaodie Gao, Shanshan Yang, Fei Sun, Xiaoya Tan, Qinmei Yang, Yue Wei, Jia Zhou, Xiaodie Gao, Shanshan Yang, Fei |
| collection | PubMed - marine biology |
| contents | The dual mechanism of mA demethylase ALKBH5 in regulating energy metabolism during exposure to MC-LR. Sun, Xiaoya Tan, Qinmei Yang, Yue Wei, Jia Zhou, Xiaodie Gao, Shanshan Yang, Fei AlkB Homolog 5, RNA Demethylase Energy Metabolism Humans Adenosine Marine Toxins Animals Glycolysis Methylation RNA-Binding Proteins Phosphatidylinositol 3-Kinases Microcystins Exposure to MC-LR has been shown to cause multiple organ injury, particularly liver injury, and altered energy metabolism is closely linked. As an effective and efficient way to regulate biological gene expression, N(6)-methyladenosine(mA) modification plays an important role in liver injury caused by microcystin-LR(MC-LR) exposure. For the first time, we reveal the dual mechanism by which AlkB homolog 5(ALKBH5) regulates energy metabolism through an mA-YTHDF3-dependent mechanism. After MC-LR exposure, low levels of ALKBH5 increased the mA modification of Phosphoinositide-3-Kinase Regulatory Subunit 1(PIK3R1) and mA methylation was located at A1557. PIK3R1-mA was recognised by YTH N6-Methyladenosine RNA Binding Protein F3(YTHDF3), which reduced the stability of PIK3R1 RNA, thereby inhibiting PIK3R1 expression and ultimately promoting glycolysis. In concert, low-level ALKBH5 inhibit oxidative phosphorylation by down-regulating the expression of Electron Transfer Flavoprotein Dehydrogenase(ETFDH), Electron Transfer Flavoprotein Subunit Alpha(ETFA) and NADH:Ubiquinone Oxidoreductase Complex Assembly Factor 4(NDUFAF4) through an mA-YTHDF3-dependent mechanism. This dual mechanism has been shown to adversely affect cell survival in MC-LR exposed environments by significantly reducing ATP levels. This study reveals for the first time the signalling pathway and molecular mechanism of MC-LR exposure to liver injury through ALKBH5-mediated mA modification, providing new protective and therapeutic principles.Subject terms: mA modification; Oxidative phosphorylation; Glycolysis The mechanism of mA demethylase ALKBH5 in regulating energy metabolism during exposure to MC-LR. Created with BioRender.com. |
| format | Artículo científico |
| id | pubmed_40610445 |
| institution | PubMed |
| language | en |
| publishDate | 2025 |
| publisher | Cell death & disease |
| record_format | pubmed |
| spellingShingle | The dual mechanism of mA demethylase ALKBH5 in regulating energy metabolism during exposure to MC-LR. Sun, Xiaoya Tan, Qinmei Yang, Yue Wei, Jia Zhou, Xiaodie Gao, Shanshan Yang, Fei AlkB Homolog 5, RNA Demethylase Energy Metabolism Humans Adenosine Marine Toxins Animals Glycolysis Methylation RNA-Binding Proteins Phosphatidylinositol 3-Kinases Microcystins The dual mechanism of mA demethylase ALKBH5 in regulating energy metabolism during exposure to MC-LR. Sun, Xiaoya Tan, Qinmei Yang, Yue Wei, Jia Zhou, Xiaodie Gao, Shanshan Yang, Fei AlkB Homolog 5, RNA Demethylase Energy Metabolism Humans Adenosine Marine Toxins Animals Glycolysis Methylation RNA-Binding Proteins Phosphatidylinositol 3-Kinases Microcystins Exposure to MC-LR has been shown to cause multiple organ injury, particularly liver injury, and altered energy metabolism is closely linked. As an effective and efficient way to regulate biological gene expression, N(6)-methyladenosine(mA) modification plays an important role in liver injury caused by microcystin-LR(MC-LR) exposure. For the first time, we reveal the dual mechanism by which AlkB homolog 5(ALKBH5) regulates energy metabolism through an mA-YTHDF3-dependent mechanism. After MC-LR exposure, low levels of ALKBH5 increased the mA modification of Phosphoinositide-3-Kinase Regulatory Subunit 1(PIK3R1) and mA methylation was located at A1557. PIK3R1-mA was recognised by YTH N6-Methyladenosine RNA Binding Protein F3(YTHDF3), which reduced the stability of PIK3R1 RNA, thereby inhibiting PIK3R1 expression and ultimately promoting glycolysis. In concert, low-level ALKBH5 inhibit oxidative phosphorylation by down-regulating the expression of Electron Transfer Flavoprotein Dehydrogenase(ETFDH), Electron Transfer Flavoprotein Subunit Alpha(ETFA) and NADH:Ubiquinone Oxidoreductase Complex Assembly Factor 4(NDUFAF4) through an mA-YTHDF3-dependent mechanism. This dual mechanism has been shown to adversely affect cell survival in MC-LR exposed environments by significantly reducing ATP levels. This study reveals for the first time the signalling pathway and molecular mechanism of MC-LR exposure to liver injury through ALKBH5-mediated mA modification, providing new protective and therapeutic principles.Subject terms: mA modification; Oxidative phosphorylation; Glycolysis The mechanism of mA demethylase ALKBH5 in regulating energy metabolism during exposure to MC-LR. Created with BioRender.com. |
| title | The dual mechanism of mA demethylase ALKBH5 in regulating energy metabolism during exposure to MC-LR. |
| topic | AlkB Homolog 5, RNA Demethylase Energy Metabolism Humans Adenosine Marine Toxins Animals Glycolysis Methylation RNA-Binding Proteins Phosphatidylinositol 3-Kinases Microcystins |
| url | https://pubmed.ncbi.nlm.nih.gov/40610445/ |