Hoeks 2012 J Cell Physiol: Difference between revisions
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|area=Respiration | |||
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|preparations=Isolated mitochondria | |preparations=Isolated mitochondria | ||
|injuries=Oxidative stress;RONS | |injuries=Oxidative stress;RONS | ||
|instruments=Oxygraph-2k | |couplingstates=LEAK, OXPHOS, ETS | ||
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Revision as of 15:18, 26 February 2016
Hoeks J, Arany Z, Phielix E, Moonen-Kornips E, Hesselink MK, Schrauwen P (2012) Enhanced lipid -but not carbohydrate- supported mitochondrial respiration in skeletal muscle of PGC-1ฮฑ overexpressing mice. J Cell Physiol 227:1026-33. |
Hoeks J, Arany Z, Phielix E, Moonen-Kornips E, Hesselink MK, Schrauwen P (2012) J Cell Physiol
Abstract: Skeletal muscle mitochondrial dysfunction has been linked to several disease states as well as the process of aging. A possible factor involved is the peroxisome proliferator-activated receptor (PPAR) ฮณ co-activator 1ฮฑ (PGC-1ฮฑ), a major player in the regulation of skeletal muscle mitochondrial metabolism. However, it is currently unknown whether PGC-1ฮฑ, besides stimulating mitochondrial proliferation, also affects the functional capacity per mitochondrion. Therefore, we here tested whether PGC-1ฮฑ overexpression, besides increasing mitochondrial content, also leads to intrinsic mitochondrial adaptations. Skeletal muscle mitochondria from 10 male, muscle-specific PGC-1ฮฑ overexpressing mice (PGC-1ฮฑTg) and 8 wild-type (WT) mice were isolated. Equal mitochondrial quantities were then analyzed for their oxidative capacity by high-resolution respirometry, fuelled by a carbohydrate-derived (pyruvate) and a lipid (palmitoyl-CoA plus carnitine) substrate. Additionally, mitochondria were tested for reactive oxygen species (superoxide) production and fatty acid (FA)-induced uncoupling. PGC-1ฮฑTg mitochondria were characterized by an improved intrinsic mitochondrial fat oxidative capacity as evidenced by pronounced increase in ADP-stimulated respiration (pโ<โ0.001) and maximal uncoupled respiration (pโ<โ0.001) upon palmitoyl-CoA plus carnitine. Interestingly, intrinsic mitochondrial capacity on a carbohydrate-derived substrate tended to be reduced. Furthermore, the sensitivity to FA-induced uncoupling was diminished in PGC-1ฮฑTg mitochondria (pโ=โ0.02) and this was accompanied by a blunted reduction in mitochondrial ROS production upon fatty acids in PGC-1ฮฑTg vs. WT mitochondria (pโ=โ0.04). Uncoupling protein 3 (UCP3) levels were markedly reduced in PGC-1ฮฑTg mitochondria (pโ<โ0.001). Taken together, in addition to stimulating mitochondrial proliferation in skeletal muscle, we show here that overexpression of PGC-1ฮฑ leads to intrinsic mitochondrial adaptations that seem restricted to fat metabolism. โข Keywords: Skeletal muscle, Mitochondria, Fat metabolism, ROS, Mitochondrial uncoupling
โข O2k-Network Lab: NL Maastricht Schrauwen P
Labels: MiParea: Respiration
Stress:Oxidative stress;RONS Organism: Mouse Tissue;cell: Skeletal muscle Preparation: Isolated mitochondria
Coupling state: LEAK, OXPHOS, ETS"ETS" is not in the list (LEAK, ROUTINE, OXPHOS, ET) of allowed values for the "Coupling states" property.
HRR: Oxygraph-2k, O2k-Protocol