Hyperglycemia-Driven Inhibition of AMP-Activated Protein Kinase α2 Induces Diabetic Cardiomyopathy by Promoting Mitochondria-Associated Endoplasmic Reticulum Membranes In Vivo

• Published in: Circulation (New York, N.Y.) Vol. 139; no. 16; pp. 1913 - 1936
• Main Authors: Wu, Shengnan, Lu, Qiulun, Ding, Ye, Wu, Yin, Qiu, Yu, Wang, Pei, Mao, Xiaoxiang, Huang, Kai, Xie, Zhonglin, Zou, Ming-Hui
• Format: Journal Article
• Language: English
• Published: United States by the American College of Cardiology Foundation and the American Heart Association, Inc 16.04.2019
• Subjects: Adult; Aged; AMP-Activated Protein Kinases - genetics; AMP-Activated Protein Kinases - metabolism; Animals; Calcium Signaling; Cell Line; Diabetic Cardiomyopathies - metabolism; Diabetic Cardiomyopathies - pathology; Endoplasmic Reticulum - metabolism; Endoplasmic Reticulum - ultrastructure; Female; Gene Expression Regulation; Humans; Male; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Middle Aged; Mitochondria - physiology; Mitochondrial Membranes - metabolism; Mitochondrial Membranes - ultrastructure; Mitochondrial Proteins - genetics; Mitochondrial Proteins - metabolism; Myocardial Contraction - genetics; Myocytes, Cardiac - physiology; Rats; FUN14 domain containing 1; mitochondria-associated endoplasmic reticulum membranes; AMP-activated protein kinase; cardiomyopathies

BACKGROUND:Fundc1 (FUN14 domain containing 1), an outer mitochondrial membrane protein, is important for mitophagy and mitochondria-associated endoplasmic reticulum membranes (MAMs). The roles of Fundc1 and MAMs in diabetic hearts remain unknown. The aims of this study, therefore, were to determine...