Sucrose non-fermenting related kinase enzyme is essential for cardiac metabolism

• DOI: 10.1242/bio.20149811
• Publication Date: 2014-12-13T03:27:40Z
• Authors: Stephanie M. Coss...; Adam J. Gastonguay; Xiaoping Bao; Alexandra Lerch-G...; Ling Zhong; Leanne M. Harmann; Christopher Koceja; Robert Q. Miao; Padmanabhan Vakeel; Changzoon Chun; Keguo Li; Jamie Foeckler; Michelle Bordas; Hartmut Weiler; Jennifer Strande; Sean P. Palecek; Ramani Ramchandran
• Keywords: 0301 basic medicine; 0303 health sciences; tie2; QH301-705.5; SNRK; Science; 4. Education; Q; 3. Good health; 03 medical and health sciences; Metabolism; Fatty acid oxidation; Biology (General); Cardiac; Research Article

ABSTRACT In this study, we have identified a novel member of the AMPK family, namely Sucrose non-fermenting related kinase (Snrk), that is responsible for maintaining cardiac metabolism in mammals. SNRK is expressed in the heart, and brain, and in cell types such as endothelial cells, smooth muscle cells and cardiomyocytes (CMs). Snrk knockout (KO) mice display enlarged hearts, and die at postnatal day 0. Microarray analysis of embryonic day 17.5 Snrk hearts, and blood profile of neonates display defect in lipid metabolic pathways. SNRK knockdown CMs showed altered phospho-acetyl-coA carboxylase and phospho-AMPK levels similar to global and endothelial conditional KO mouse. Finally, adult cardiac conditional KO mouse displays severe cardiac functional defects and lethality. Our results suggest that Snrk is essential for maintaining cardiac metabolic homeostasis, and shows an autonomous role for SNRK during mammalian development.