Journal article
MuRF1 activity is present in cardiac mitochondria and regulates reactive oxygen species production in vivo
Journal of bioenergetics and biomembranes, Vol.46(3), pp.173-187
06/2014
DOI: 10.1007/s10863-014-9549-9
PMCID: PMC4047114
PMID: 24733503
Abstract
MuRF1 is a previously reported ubiquitin-ligase found in striated muscle that targets troponin I and myosin heavy chain for degradation. While MuRF1 has been reported to interact with mitochondrial substrates in yeast two-hybrid studies, no studies have identified MuRF1’s role in regulating mitochondrial function to date. In the present study, we measured cardiac mitochondrial function from isolated permeabilized muscle fibers in previously phenotyped MuRF1 transgenic and MuRF1−/− mouse models to determine the role of MuRF1 in intermediate energy metabolism and ROS production. We identified a significant decrease in reactive oxygen species production in cardiac muscle fibers from MuRF1 transgenic mice with increased alpha-MHC driven MuRF1 expression. Increased MuRF1 expression in
ex vivo
and
in vitro
experiments revealed no alterations in the respiratory chain complex I and II function. Working perfusion experiments on MuRF1 transgenic hearts demonstrated significant changes in glucose or oleate oxidation; however, total oxygen consumption was decreased. This data provides evidence for MuRF1 as a novel regulator of cardiac ROS, offering another mechanism by which increased MuRF1 expression may be cardioprotective in ischemia reperfusion injury, in addition to its inhibition of apoptosis via proteasome-mediate degradation of c-Jun. The lack of mitochondrial function phenotype identified in MuRF1−/− hearts may be due to the overlapping interactions of MuRF1 and MuRF2 with energy regulating proteins found by yeast two-hybrid studies reported here, implying a duplicity in MuRF1 and MuRF2’s regulation of mitochondrial function.
Details
- Title: Subtitle
- MuRF1 activity is present in cardiac mitochondria and regulates reactive oxygen species production in vivo
- Creators
- Taylor A Mattox - Department of Pharmacology, East Carolina University, Greenville, NC USAMartin E Young - Division of Cardiovascular Diseases, Department of Medicine, University of Alabama at Birmingham, Birmingham, ALCarrie E Rubel - Department of Pharmacology, University of North Carolina, Chapel Hill, NC USACarolyn Spaniel - Department of Pathology & Laboratory Medicine, University of North Carolina, Chapel Hill, NC USAJessica E Rodríguez - Department of Pathology & Laboratory Medicine, University of North Carolina, Chapel Hill, NC USATrisha J Grevengoed - Department of Nutrition, University of North Carolina, Chapel Hill, NC USAMathias Gautel - Cardiovascular Division and Randall Division for Cell and Molecular, King’s College London BHF Centre of Research Excellence, Biophysics, London SE1 1UL, UKZhelong Xu - Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin 300070, ChinaEthan J Anderson - Department of Pharmacology, East Carolina University, Greenville, NC USAMonte S Willis - Department of Pathology & Laboratory Medicine, University of North Carolina, Chapel Hill, NC USA
- Resource Type
- Journal article
- Publication Details
- Journal of bioenergetics and biomembranes, Vol.46(3), pp.173-187
- DOI
- 10.1007/s10863-014-9549-9
- PMID
- 24733503
- PMCID
- PMC4047114
- NLM abbreviation
- J Bioenerg Biomembr
- ISSN
- 0145-479X
- eISSN
- 1573-6881
- Publisher
- Springer Science and Business Media LLC
- Language
- English
- Date published
- 06/2014
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics; Fraternal Order of Eagles Diabetes Research Center; Health, Sport, and Human Physiology
- Record Identifier
- 9984065310002771
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