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McBride 2019 Arch Biochem Biophys
Additional label 2019-01  + , Amplex UltraRed  +
Coupling states LEAK  + , OXPHOS  +
Enzyme Uncoupling protein  +
Has abstract Mitochondrial reactive oxygen species (ROS
Mitochondrial reactive oxygen species (ROS) are important cellular signaling molecules, but can cause oxidative damage if not kept within tolerable limits. An important proximal form of ROS in mitochondria is superoxide. Its production is thought to occur in regulated stochastic bursts, but current methods using mitochondrial targeted cpYFP to assess superoxide flashes are confounded by changes in pH. Accordingly, these flashes are generally referred to as 'mitoflashes'. Here we provide regulatory insights into mitoflashes and pH fluctuations in skeletal muscle, and the role of uncoupling protein-3 (UCP3). Using quantitative confocal microscopy of mitoflashes in intact muscle fibers, we show that the mitoflash magnitude significantly correlates with the degree of mitochondrial inner membrane depolarization and ablation of UCP3 did not affect this correlation. We assessed the effects of the absence of UCP3 on mitoflash activity in intact skeletal muscle fibers, and found no effects on mitoflash frequency, amplitude or duration, with a slight reduction in the average size of mitoflashes. We further investigated the regulation of pH flashes (pHlashes, presumably a component of mitoflash) by UCP3 using mitochondrial targeted SypHer (mt-SypHer) in skeletal muscle fibers. The frequency of pHlashes was significantly reduced in the absence of UCP3, without changes in other flash properties. ROS scavenger, tiron, did not alter pHlash frequency in either WT or UCP3KO mice. High resolution respirometry revealed that in the absence of UCP3 there is impaired proton leak and Complex I-driven respiration and maximal coupled respiration. Total cellular production of hydrogen peroxide (H2O2) as detected by Amplex-UltraRed was unaffected. Altogether, we demonstrate a correlation between mitochondrial membrane potential and mitoflash magnitude in skeletal muscle fibers that is independent of UCP3 and a role for UCP3 in the control of pHlash frequency and of proton leak- and Complex I coupled-respiration in skeletal muscle fibers. The differential regulation of mitoflashes and pHlashes by UCP3 and tiron also indicate that the two events, though may be related, are not identical events. <small>Copyright © 2019. Published by Elsevier Inc.</small>
. Published by Elsevier Inc.</small>  +
Has editor [[Plangger M]]  +
Has info [ PMID: 30659802]  +
Has publicationkeywords Electron transport chain  + , Mitochondrial flashes  + , Proton leak  + , Reactive oxygen species  + , Superoxide  + , Uncoupling protein 3  + , pH  +
Has title McBride S, Wei-LaPierre L, McMurray F, MacFarlane M, Qiu X, Patten DA, Dirksen RT, Harper ME (2019) Skeletal muscle mitoflashes, pH, and the role of uncoupling protein-3. Arch Biochem Biophys 663:239-48.  +
Instrument and method O2k-Fluorometer  + , Oxygraph-2k  +
Mammal and model Mouse  +
MiP area Genetic knockout;overexpression  + , Respiration  +
Pathways CIV  + , F  + , N  + , NS  + , ROX  +
Preparation Permeabilized tissue  +
Respiration and regulation pH  +
Stress Oxidative stress;RONS  +
Tissue and cell Skeletal muscle  +
Was published by MiPNetLab CA Ottawa Harper ME +
Was published in journal Arch Biochem Biophys +
Was published in year 2019  +
Was written by McBride S + , Wei-LaPierre L + , McMurray F + , MacFarlane M + , Qiu X + , Patten DA + , Dirksen RT + , Harper ME +
Categories Publications
Modification date
"Modification date" is a predefined property that corresponds to the date of the last modification of a subject and is provided by Semantic MediaWiki.
09:56:31, 23 May 2019  +
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