Journal article
Snf1-related kinase improves cardiac mitochondrial efficiency and decreases mitochondrial uncoupling
Nature communications, Vol.8(1), pp.14095-14095
01/24/2017
DOI: 10.1038/ncomms14095
PMCID: PMC5286102
PMID: 28117339
Abstract
Ischaemic heart disease limits oxygen and metabolic substrate availability to the heart, resulting in tissue death. Here, we demonstrate that the AMP-activated protein kinase (AMPK)-related protein Snf1-related kinase (SNRK) decreases cardiac metabolic substrate usage and mitochondrial uncoupling, and protects against ischaemia/reperfusion. Hearts from transgenic mice overexpressing SNRK have decreased glucose and palmitate metabolism and oxygen consumption, but maintained power and function. They also exhibit decreased uncoupling protein 3 (UCP3) and mitochondrial uncoupling. Conversely, Snrk knockout mouse hearts have increased glucose and palmitate oxidation and UCP3. SNRK knockdown in cardiac cells decreases mitochondrial efficiency, which is abolished with UCP3 knockdown. We show that Tribbles homologue 3 (Trib3) binds to SNRK, and downregulates UCP3 through PPARα. Finally, SNRK is increased in cardiomyopathy patients, and SNRK reduces infarct size after ischaemia/reperfusion. SNRK also decreases cardiac cell death in a UCP3-dependent manner. Our results suggest that SNRK improves cardiac mitochondrial efficiency and ischaemic protection.
Details
- Title: Subtitle
- Snf1-related kinase improves cardiac mitochondrial efficiency and decreases mitochondrial uncoupling
- Creators
- Amy K Rines - Feinberg Cardiovascular Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USAHsiang-Chun Chang - Feinberg Cardiovascular Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USARongxue Wu - Feinberg Cardiovascular Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USATatsuya Sato - Feinberg Cardiovascular Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USAArineh Khechaduri - Feinberg Cardiovascular Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USAHidemichi Kouzu - Feinberg Cardiovascular Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USAJason Shapiro - Feinberg Cardiovascular Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USAMeng Shang - Feinberg Cardiovascular Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USAMichael A Burke - Feinberg Cardiovascular Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USAEltyeb Abdelwahid - Feinberg Cardiovascular Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USAXinghang Jiang - Feinberg Cardiovascular Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USAChunlei Chen - Feinberg Cardiovascular Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USATenley A Rawlings - Division of Endocrinology, Metabolism, and Diabetes and Program in Molecular Medicine, University of Utah, School of Medicine, Salt Lake City, Utah 84132, USAGary D Lopaschuk - University of AlbertaPaul T Schumacker - Feinberg Cardiovascular Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USAE Dale Abel - Division of Endocrinology, Metabolism, and Diabetes and Program in Molecular Medicine, University of Utah, School of Medicine, Salt Lake City, Utah 84132, USAHossein Ardehali - Feinberg Cardiovascular Research Institute, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA
- Resource Type
- Journal article
- Publication Details
- Nature communications, Vol.8(1), pp.14095-14095
- DOI
- 10.1038/ncomms14095
- PMID
- 28117339
- PMCID
- PMC5286102
- NLM abbreviation
- Nat Commun
- ISSN
- 2041-1723
- eISSN
- 2041-1723
- Publisher
- England
- Grant note
- R01 HL087149 / National Heart, Lung, and Blood Institute R01 HL138982 / National Heart, Lung, and Blood Institute R01 HL104181 / National Heart, Lung, and Blood Institute T32 GM008152 / National Institute of General Medical Sciences K02 HL107448 / National Heart, Lung, and Blood Institute R01 HL140973 / National Heart, Lung, and Blood Institute P01 HL108795 / National Heart, Lung, and Blood Institute R01 HL127646 / National Heart, Lung, and Blood Institute R01 HL108379 / National Heart, Lung, and Blood Institute
- Language
- English
- Date published
- 01/24/2017
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984025268602771
Metrics
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