Mitochondria as an important target of metformin: The mechanism of action, toxic and side effects, and new therapeutic applications
Metformin is the oldest and most commonly used first-line antidiabetic drug because of its good clinical efficacy, high safety, low cost and easy access. At the same time, in recent years, we have found that its role as a therapeutic drug is gradually expanding. A large number of basic studies have...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-03-01
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| Series: | Pharmacological Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1043661822000597 |
| _version_ | 1797366645680766976 |
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| author | Jin Feng Xiaohui Wang Xiaochun Ye Irma Ares Bernardo Lopez-Torres Marta Martínez María-Rosa Martínez-Larrañaga Xu Wang Arturo Anadón María-Aránzazu Martínez |
| author_facet | Jin Feng Xiaohui Wang Xiaochun Ye Irma Ares Bernardo Lopez-Torres Marta Martínez María-Rosa Martínez-Larrañaga Xu Wang Arturo Anadón María-Aránzazu Martínez |
| author_sort | Jin Feng |
| collection | DOAJ |
| description | Metformin is the oldest and most commonly used first-line antidiabetic drug because of its good clinical efficacy, high safety, low cost and easy access. At the same time, in recent years, we have found that its role as a therapeutic drug is gradually expanding. A large number of basic studies have shown that metformin may become a promising attractive candidate for drug repurposing. Therefore, it is extremely beneficial to conduct an in-depth discussion on the main mechanism of metformin. As early as the year 1950, studies showed that metformin played a biological role by regulating mitochondria. Then, ground-breaking studies showed that metformin functions by inhibiting complex I in the mitochondrial respiratory chain. Although there are still many controversies about the key molecular targets of metformin, with the emergence of more and more evidence, it gradually came to be concluded that mitochondria play a central role in the application of metformin. Mitochondria are important fulcrums for cell functions. The exact mechanism of action in mitochondria of this pleiotropic anti-hyperglycaemic molecule is still unclear. This review article explores the core role of mitochondria in the pharmacological and toxicological effects of metformin, and summarises the mechanism of action if metformin in mitochondria. It also provides ideas and supporting evidence for the re-development and reuse of metformin as an old drug, as well as new insight into the treatment of human diseases. |
| first_indexed | 2024-03-08T17:06:41Z |
| format | Article |
| id | doaj.art-357dabd5f11640feaf9dc3d262cb6459 |
| institution | Directory Open Access Journal |
| issn | 1096-1186 |
| language | English |
| last_indexed | 2024-03-08T17:06:41Z |
| publishDate | 2022-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Pharmacological Research |
| spelling | doaj.art-357dabd5f11640feaf9dc3d262cb64592024-01-04T04:36:25ZengElsevierPharmacological Research1096-11862022-03-01177106114Mitochondria as an important target of metformin: The mechanism of action, toxic and side effects, and new therapeutic applicationsJin Feng0Xiaohui Wang1Xiaochun Ye2Irma Ares3Bernardo Lopez-Torres4Marta Martínez5María-Rosa Martínez-Larrañaga6Xu Wang7Arturo Anadón8María-Aránzazu Martínez9National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, Hubei 430070, China; MAO Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, Hubei 430070, ChinaNational Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, Hubei 430070, ChinaNational Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, Hubei 430070, China; MAO Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, Hubei 430070, ChinaDepartment of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Universidad Complutense de Madrid (UCM), and Research Institute Hospital 12 de Octubre (i+12), 28040 Madrid, SpainDepartment of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Universidad Complutense de Madrid (UCM), and Research Institute Hospital 12 de Octubre (i+12), 28040 Madrid, SpainDepartment of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Universidad Complutense de Madrid (UCM), and Research Institute Hospital 12 de Octubre (i+12), 28040 Madrid, SpainDepartment of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Universidad Complutense de Madrid (UCM), and Research Institute Hospital 12 de Octubre (i+12), 28040 Madrid, SpainNational Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, Hubei 430070, China; MAO Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, Hubei 430070, China; Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Universidad Complutense de Madrid (UCM), and Research Institute Hospital 12 de Octubre (i+12), 28040 Madrid, Spain; Correspondence to: National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Wuhan, Hubei 430070, China.Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Universidad Complutense de Madrid (UCM), and Research Institute Hospital 12 de Octubre (i+12), 28040 Madrid, Spain; Correspondence to: Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain.Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Universidad Complutense de Madrid (UCM), and Research Institute Hospital 12 de Octubre (i+12), 28040 Madrid, SpainMetformin is the oldest and most commonly used first-line antidiabetic drug because of its good clinical efficacy, high safety, low cost and easy access. At the same time, in recent years, we have found that its role as a therapeutic drug is gradually expanding. A large number of basic studies have shown that metformin may become a promising attractive candidate for drug repurposing. Therefore, it is extremely beneficial to conduct an in-depth discussion on the main mechanism of metformin. As early as the year 1950, studies showed that metformin played a biological role by regulating mitochondria. Then, ground-breaking studies showed that metformin functions by inhibiting complex I in the mitochondrial respiratory chain. Although there are still many controversies about the key molecular targets of metformin, with the emergence of more and more evidence, it gradually came to be concluded that mitochondria play a central role in the application of metformin. Mitochondria are important fulcrums for cell functions. The exact mechanism of action in mitochondria of this pleiotropic anti-hyperglycaemic molecule is still unclear. This review article explores the core role of mitochondria in the pharmacological and toxicological effects of metformin, and summarises the mechanism of action if metformin in mitochondria. It also provides ideas and supporting evidence for the re-development and reuse of metformin as an old drug, as well as new insight into the treatment of human diseases.http://www.sciencedirect.com/science/article/pii/S1043661822000597MetforminAntidiabetic drugMitochondrial complex IOxidative stressMultiple therapeutic usesToxic and side effects |
| spellingShingle | Jin Feng Xiaohui Wang Xiaochun Ye Irma Ares Bernardo Lopez-Torres Marta Martínez María-Rosa Martínez-Larrañaga Xu Wang Arturo Anadón María-Aránzazu Martínez Mitochondria as an important target of metformin: The mechanism of action, toxic and side effects, and new therapeutic applications Pharmacological Research Metformin Antidiabetic drug Mitochondrial complex I Oxidative stress Multiple therapeutic uses Toxic and side effects |
| title | Mitochondria as an important target of metformin: The mechanism of action, toxic and side effects, and new therapeutic applications |
| title_full | Mitochondria as an important target of metformin: The mechanism of action, toxic and side effects, and new therapeutic applications |
| title_fullStr | Mitochondria as an important target of metformin: The mechanism of action, toxic and side effects, and new therapeutic applications |
| title_full_unstemmed | Mitochondria as an important target of metformin: The mechanism of action, toxic and side effects, and new therapeutic applications |
| title_short | Mitochondria as an important target of metformin: The mechanism of action, toxic and side effects, and new therapeutic applications |
| title_sort | mitochondria as an important target of metformin the mechanism of action toxic and side effects and new therapeutic applications |
| topic | Metformin Antidiabetic drug Mitochondrial complex I Oxidative stress Multiple therapeutic uses Toxic and side effects |
| url | http://www.sciencedirect.com/science/article/pii/S1043661822000597 |
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