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AGO2 Protects Against Diabetic Cardiomyopathy by Activating Mitochondrial Gene Translation.
Zhan, Jiabing; Jin, Kunying; Xie, Rong; Fan, Jiahui; Tang, Yuyan; Chen, Chen; Li, Huaping; Wang, Dao Wen.
Afiliación
  • Zhan J; Division of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (J.Z., K.J., R.X., J.F., Y.T., C.C., H.L., D.W.W.).
  • Jin K; Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan, China (J.Z.).
  • Xie R; Department of Cardiology, Fujian Medical Center for Cardiovascular Diseases, Fujian Institute of Coronary Heart Disease, Fujian Medical University, China (J.Z.).
  • Fan J; Division of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (J.Z., K.J., R.X., J.F., Y.T., C.C., H.L., D.W.W.).
  • Tang Y; Division of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (J.Z., K.J., R.X., J.F., Y.T., C.C., H.L., D.W.W.).
  • Chen C; Division of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (J.Z., K.J., R.X., J.F., Y.T., C.C., H.L., D.W.W.).
  • Li H; Division of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (J.Z., K.J., R.X., J.F., Y.T., C.C., H.L., D.W.W.).
  • Wang DW; Division of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (J.Z., K.J., R.X., J.F., Y.T., C.C., H.L., D.W.W.).
Circulation ; 149(14): 1102-1120, 2024 04 02.
Article en En | MEDLINE | ID: mdl-38126189
ABSTRACT

BACKGROUND:

Diabetes is associated with cardiovascular complications. microRNAs translocate into subcellular organelles to modify genes involved in diabetic cardiomyopathy. However, functional properties of subcellular AGO2 (Argonaute2), a core member of miRNA machinery, remain elusive.

METHODS:

We elucidated the function and mechanism of subcellular localized AGO2 on mouse models for diabetes and diabetic cardiomyopathy. Recombinant adeno-associated virus type 9 was used to deliver AGO2 to mice through the tail vein. Cardiac structure and functions were assessed by echocardiography and catheter manometer system.

RESULTS:

AGO2 was decreased in mitochondria of diabetic cardiomyocytes. Overexpression of mitochondrial AGO2 attenuated diabetes-induced cardiac dysfunction. AGO2 recruited TUFM, a mitochondria translation elongation factor, to activate translation of electron transport chain subunits and decrease reactive oxygen species. Malonylation, a posttranslational modification of AGO2, reduced the importing of AGO2 into mitochondria in diabetic cardiomyopathy. AGO2 malonylation was regulated by a cytoplasmic-localized short isoform of SIRT3 through a previously unknown demalonylase function.

CONCLUSIONS:

Our findings reveal that the SIRT3-AGO2-CYTB axis links glucotoxicity to cardiac electron transport chain imbalance, providing new mechanistic insights and the basis to develop mitochondria targeting therapies for diabetic cardiomyopathy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: MicroARNs / Diabetes Mellitus / Sirtuina 3 / Cardiomiopatías Diabéticas Límite: Animals Idioma: En Revista: Circulation Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: MicroARNs / Diabetes Mellitus / Sirtuina 3 / Cardiomiopatías Diabéticas Límite: Animals Idioma: En Revista: Circulation Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos