Sirtuin 1 suppresses mitochondrial dysfunction of ischemic mouse livers in a mitofusin 2-dependent manner
| العنوان: | Sirtuin 1 suppresses mitochondrial dysfunction of ischemic mouse livers in a mitofusin 2-dependent manner |
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| المؤلفون: | Kevin E. Behrns, Brian K. Law, William A. Dunn, Kristina L. Go, Ivan Zendejas, Joseph Flores-Toro, Sooyeon Lee, Joseph W. Dean, Mary E. Law, Jae-Sung Kim, M. H. Lee, Thomas G. Biel |
| المصدر: | Cell Death & Differentiation. 23:279-290 |
| بيانات النشر: | Springer Science and Business Media LLC, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, medicine.medical_specialty, endocrine system diseases, MFN2, Ischemia, Mitochondria, Liver, Biology, Mitochondrion, Mitochondrial Membrane Transport Proteins, GTP Phosphohydrolases, 03 medical and health sciences, Sirtuin 1, Internal medicine, Autophagy, medicine, Animals, Humans, MFN1, Protein Interaction Domains and Motifs, Molecular Biology, Mice, Knockout, Original Paper, Calpain, Mitochondrial Permeability Transition Pore, food and beverages, Cell Biology, medicine.disease, Mice, Inbred C57BL, enzymes and coenzymes (carbohydrates), 030104 developmental biology, medicine.anatomical_structure, Endocrinology, Liver, Mitochondrial permeability transition pore, Reperfusion Injury, Hepatocyte, Immunology, biology.protein, lipids (amino acids, peptides, and proteins), hormones, hormone substitutes, and hormone antagonists |
| الوصف: | Ischemia/reperfusion (I/R) injury is a major cause of morbidity and mortality after liver surgery. The role of Sirtuin 1 (SIRT1) in hepatic I/R injury remains elusive. Using human and mouse livers, we investigated the effects of I/R on hepatocellular SIRT1. SIRT1 expression was significantly decreased after I/R. Genetic overexpression or pharmacological activation of SIRT1 markedly suppressed defective autophagy, onset of the mitochondrial permeability transition, and hepatocyte death after I/R, whereas SIRT1-null hepatocytes exhibited increased sensitivity to I/R injury. Biochemical approaches revealed that SIRT1 interacts with mitofusin-2 (MFN2). Furthermore, MFN2, but not MFN1, was deacetylated by SIRT1. Moreover, SIRT1 overexpression substantially increased autophagy in wild-type cells, but not in MFN2-deficient cells. Thus, our results demonstrate that the loss of SIRT1 causes a sequential chain of defective autophagy, mitochondrial dysfunction, and hepatocyte death after I/R. |
| تدمد: | 1476-5403 1350-9047 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::53a59eea1fd1311dcee7cadb6ada044dTest https://doi.org/10.1038/cdd.2015.96Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....53a59eea1fd1311dcee7cadb6ada044d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14765403 13509047 |
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