Browsing by Subject "Mitochondria, Heart"

Now showing 1 - 4 of 4
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    Increased COUP-TFII expression in adult hearts induces mitochondrial dysfunction resulting in heart failure
    (Springer Nature, 2015-09-10) Wu, San-Pin; Kao, Chung-Yang; Wang, Leiming; Creighton, Chad J.; Yang, Jin; Donti, Taraka R.; Harmancey, Romain; Vasquez, Hernan G.; Graham, Brett H.; Bellen, Hugo J.; Taegtmeyer, Heinrich; Chang, Ching-Pin; Tsai, Ming-Jer; Tsai, Sophia Y.; Department of Medicine, IU School of Medicine
    Mitochondrial dysfunction and metabolic remodelling are pivotal in the development of cardiomyopathy. Here, we show that myocardial COUP-TFII overexpression causes heart failure in mice, suggesting a causal effect of elevated COUP-TFII levels on development of dilated cardiomyopathy. COUP-TFII represses genes critical for mitochondrial electron transport chain enzyme activity, oxidative stress detoxification and mitochondrial dynamics, resulting in increased levels of reactive oxygen species and lower rates of oxygen consumption in mitochondria. COUP-TFII also suppresses the metabolic regulator PGC-1 network and decreases the expression of key glucose and lipid utilization genes, leading to a reduction in both glucose and oleate oxidation in the hearts. These data suggest that COUP-TFII affects mitochondrial function, impairs metabolic remodelling and has a key role in dilated cardiomyopathy. Last, COUP-TFII haploinsufficiency attenuates the progression of cardiac dilation and improves survival in a calcineurin transgenic mouse model, indicating that COUP-TFII may serve as a therapeutic target for the treatment of dilated cardiomyopathy.
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    Mitochondrial Ca2+ Uniporter and CaMKII in heart
    (Nature Publishing Group, 2014-09-25) Fieni, Francesca; Johnson, Derrick E.; Hudmon, Andy; Kirichok, Yuriy; Department of Biochemistry & Molecular Biology, IU School of Medicine
    The influx of cytosolic Ca2+ into mitochondria is mediated primarily by the mitochondrial calcium uniporter (MCU), a small-conductance, Ca2+-selective channel-. MCU modulates intracellular Ca2+ transients and regulates ATP production and cell death. Recently, Joiner et al. reported that MCU is regulated by mitochondrial CaMKII, and this regulation determines stress response in heart. They reported a very large current putatively mediated by MCU that was about two orders of magnitude greater than the MCU current (IMCU) that we previously measured in heart mitochondria. Also, the current traces presented by Joiner et al. showed unusually high fluctuations incompatible with the low single-channel conductance of MCU. Here we performed patch-clamp recordings from mouse heart mitochondria under the exact conditions used by Joiner et al. We confirmed that IMCU in cardiomyocytes is very small and showed that it is not directly regulated by CaMKII. Thus the currents presented by Joiner et al. do not correspond to MCU, and there is no direct electrophysiological evidence that CaMKII regulates MCU.