Noncoupled Mitochondrial Respiration as Therapeutic Approach for the Treatment of Metabolic Diseases: Focus on Transgenic Animal Models
Mitochondrial dysfunction contributes to numerous chronic diseases, and mitochondria are targets for various toxins and xenobiotics. Therefore, the development of drugs or therapeutic strategies targeting mitochondria is an important task in modern medicine. It is well known that the primary, althou...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/22/16491 |
| _version_ | 1797458931539247104 |
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| author | Artem P. Gureev Alina A. Alimova Denis N. Silachev Egor Y. Plotnikov |
| author_facet | Artem P. Gureev Alina A. Alimova Denis N. Silachev Egor Y. Plotnikov |
| author_sort | Artem P. Gureev |
| collection | DOAJ |
| description | Mitochondrial dysfunction contributes to numerous chronic diseases, and mitochondria are targets for various toxins and xenobiotics. Therefore, the development of drugs or therapeutic strategies targeting mitochondria is an important task in modern medicine. It is well known that the primary, although not the sole, function of mitochondria is ATP generation, which is achieved by coupled respiration. However, a high membrane potential can lead to uncontrolled reactive oxygen species (ROS) production and associated dysfunction. For over 50 years, scientists have been studying various synthetic uncouplers, and for more than 30 years, uncoupling proteins that are responsible for uncoupled respiration in mitochondria. Additionally, the proteins of the mitochondrial alternative respiratory pathway exist in plant mitochondria, allowing noncoupled respiration, in which electron flow is not associated with membrane potential formation. Over the past two decades, advances in genetic engineering have facilitated the creation of various cellular and animal models that simulate the effects of uncoupled and noncoupled respiration in different tissues under various disease conditions. In this review, we summarize and discuss the findings obtained from these transgenic models. We focus on the advantages and limitations of transgenic organisms, the observed physiological and biochemical changes, and the therapeutic potential of uncoupled and noncoupled respiration. |
| first_indexed | 2024-03-09T16:45:13Z |
| format | Article |
| id | doaj.art-9f7784fc8982479b8c6cc3a554087581 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T16:45:13Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-9f7784fc8982479b8c6cc3a5540875812023-11-24T14:47:54ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-11-0124221649110.3390/ijms242216491Noncoupled Mitochondrial Respiration as Therapeutic Approach for the Treatment of Metabolic Diseases: Focus on Transgenic Animal ModelsArtem P. Gureev0Alina A. Alimova1Denis N. Silachev2Egor Y. Plotnikov3Department of Genetics, Cytology and Bioengineering, Voronezh State University, 394018 Voronezh, RussiaDepartment of Genetics, Cytology and Bioengineering, Voronezh State University, 394018 Voronezh, RussiaA.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119234 Moscow, RussiaA.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119234 Moscow, RussiaMitochondrial dysfunction contributes to numerous chronic diseases, and mitochondria are targets for various toxins and xenobiotics. Therefore, the development of drugs or therapeutic strategies targeting mitochondria is an important task in modern medicine. It is well known that the primary, although not the sole, function of mitochondria is ATP generation, which is achieved by coupled respiration. However, a high membrane potential can lead to uncontrolled reactive oxygen species (ROS) production and associated dysfunction. For over 50 years, scientists have been studying various synthetic uncouplers, and for more than 30 years, uncoupling proteins that are responsible for uncoupled respiration in mitochondria. Additionally, the proteins of the mitochondrial alternative respiratory pathway exist in plant mitochondria, allowing noncoupled respiration, in which electron flow is not associated with membrane potential formation. Over the past two decades, advances in genetic engineering have facilitated the creation of various cellular and animal models that simulate the effects of uncoupled and noncoupled respiration in different tissues under various disease conditions. In this review, we summarize and discuss the findings obtained from these transgenic models. We focus on the advantages and limitations of transgenic organisms, the observed physiological and biochemical changes, and the therapeutic potential of uncoupled and noncoupled respiration.https://www.mdpi.com/1422-0067/24/22/16491transgenic model<i>Ciano intestinalis</i>noncoupled respirationalternative oxidasealternative NADH dehydrogenase |
| spellingShingle | Artem P. Gureev Alina A. Alimova Denis N. Silachev Egor Y. Plotnikov Noncoupled Mitochondrial Respiration as Therapeutic Approach for the Treatment of Metabolic Diseases: Focus on Transgenic Animal Models International Journal of Molecular Sciences transgenic model <i>Ciano intestinalis</i> noncoupled respiration alternative oxidase alternative NADH dehydrogenase |
| title | Noncoupled Mitochondrial Respiration as Therapeutic Approach for the Treatment of Metabolic Diseases: Focus on Transgenic Animal Models |
| title_full | Noncoupled Mitochondrial Respiration as Therapeutic Approach for the Treatment of Metabolic Diseases: Focus on Transgenic Animal Models |
| title_fullStr | Noncoupled Mitochondrial Respiration as Therapeutic Approach for the Treatment of Metabolic Diseases: Focus on Transgenic Animal Models |
| title_full_unstemmed | Noncoupled Mitochondrial Respiration as Therapeutic Approach for the Treatment of Metabolic Diseases: Focus on Transgenic Animal Models |
| title_short | Noncoupled Mitochondrial Respiration as Therapeutic Approach for the Treatment of Metabolic Diseases: Focus on Transgenic Animal Models |
| title_sort | noncoupled mitochondrial respiration as therapeutic approach for the treatment of metabolic diseases focus on transgenic animal models |
| topic | transgenic model <i>Ciano intestinalis</i> noncoupled respiration alternative oxidase alternative NADH dehydrogenase |
| url | https://www.mdpi.com/1422-0067/24/22/16491 |
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