Garcia-Roves 2008 J Biol Chem: Difference between revisions
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|title=Garcia-Roves PM, Osler ME, HolmstrΓΆm MH, Zierath JR (2008) Gain-of-function R225Q mutation in AMP-activated protein kinase gamma3 subunit increases mitochondrial biogenesis in glycolytic skeletal muscle. J. Biol. Chem. 283: 35724-25734. | |title=Garcia-Roves PM, Osler ME, HolmstrΓΆm MH, Zierath JR (2008) Gain-of-function R225Q mutation in AMP-activated protein kinase gamma3 subunit increases mitochondrial biogenesis in glycolytic skeletal muscle. J. Biol. Chem. 283: 35724-25734. | ||
|info=[http://www.ncbi.nlm.nih.gov/pubmed/18838377 PMID: 18838377] | |info=[http://www.ncbi.nlm.nih.gov/pubmed/18838377 PMID: 18838377] | ||
|authors=Garcia | |authors=Garcia Roves PM, Osler ME, Holmstroem MH, Zierath JR | ||
|year=2008 | |year=2008 | ||
|journal=J. Biol. Chem. | |journal=J. Biol. Chem. | ||
|abstract=AMP-activated protein kinase (AMPK) is a heterotrimeric complex, composed of a catalytic subunit (Ξ±) and two regulatory subunits (Ξ² and Ξ³), that works as a cellular energy sensor. The existence of multiple heterotrimeric complexes provides a molecular basis for the multiple roles of this highly conserved signaling system. The AMPK<sub>Ξ³3</sub> subunit is predominantly expressed in skeletal muscle, mostly in type II glycolytic fiber types. We determined whether the AMPK<sub>Ξ³3</sub> subunit has a role in signaling pathways that mediate mitochondrial biogenesis in skeletal muscle. We provide evidence that overexpression or ablation of the AMPK<sub>Ξ³3</sub> subunit does not appear to play a critical role in defining mitochondrial content in resting skeletal muscle. However, overexpression of a mutant form (R225Q) of the AMPK<sub>Ξ³3</sub> subunit (Tg-AMPK<sub>Ξ³3</sub><sup>225Q</sup>) increases mitochondrial biogenesis in glycolytic skeletal muscle. These adaptations are associated with an increase in expression of the co-activator PGC-1Ξ± and several transcription factors that regulate mitochondrial biogenesis, including NRF-1, NRF-2, and TFAM. Succinate dehydrogenase staining, a marker of the oxidative profile of individual fibers, was also increased in transversal skeletal muscle sections of white gastrocnemius muscle from Tg-AMPK<sub>Ξ³3</sub><sup>225Q</sup> mice, independent of changes in fiber type composition. In conclusion, a single nucleotide mutation (R225Q) in the AMPK gamma3 subunit is associated with mitochondrial biogenesis in glycolytic skeletal muscle, concomitant with increased expression of the co-activator PGC-1Ξ± and several transcription factors that regulate mitochondrial proteins, without altering fiber type composition. | |abstract=AMP-activated protein kinase (AMPK) is a heterotrimeric complex, composed of a catalytic subunit (Ξ±) and two regulatory subunits (Ξ² and Ξ³), that works as a cellular energy sensor. The existence of multiple heterotrimeric complexes provides a molecular basis for the multiple roles of this highly conserved signaling system. The AMPK<sub>Ξ³3</sub> subunit is predominantly expressed in skeletal muscle, mostly in type II glycolytic fiber types. We determined whether the AMPK<sub>Ξ³3</sub> subunit has a role in signaling pathways that mediate mitochondrial biogenesis in skeletal muscle. We provide evidence that overexpression or ablation of the AMPK<sub>Ξ³3</sub> subunit does not appear to play a critical role in defining mitochondrial content in resting skeletal muscle. However, overexpression of a mutant form (R225Q) of the AMPK<sub>Ξ³3</sub> subunit (Tg-AMPK<sub>Ξ³3</sub><sup>225Q</sup>) increases mitochondrial biogenesis in glycolytic skeletal muscle. These adaptations are associated with an increase in expression of the co-activator PGC-1Ξ± and several transcription factors that regulate mitochondrial biogenesis, including NRF-1, NRF-2, and TFAM. Succinate dehydrogenase staining, a marker of the oxidative profile of individual fibers, was also increased in transversal skeletal muscle sections of white gastrocnemius muscle from Tg-AMPK<sub>Ξ³3</sub><sup>225Q</sup> mice, independent of changes in fiber type composition. In conclusion, a single nucleotide mutation (R225Q) in the AMPK gamma3 subunit is associated with mitochondrial biogenesis in glycolytic skeletal muscle, concomitant with increased expression of the co-activator PGC-1Ξ± and several transcription factors that regulate mitochondrial proteins, without altering fiber type composition. | ||
|discipline=Mitochondrial Physiology, Biomedicine | |||
}} | }} | ||
{{Labeling | {{Labeling | ||
| | |instruments=Oxygraph-2k | ||
|injuries=Genetic Defect; Knockdown; Overexpression | |injuries=Genetic Defect; Knockdown; Overexpression | ||
|tissues=Skeletal Muscle | |tissues=Skeletal Muscle | ||
|topics=Respiration; OXPHOS; ETS Capacity, Mitochondrial Biogenesis; Mitochondrial Density | |topics=Respiration; OXPHOS; ETS Capacity, Mitochondrial Biogenesis; Mitochondrial Density | ||
| | |discipline=Mitochondrial Physiology, Biomedicine | ||
}} | }} | ||
Revision as of 15:51, 1 August 2011
| Garcia-Roves PM, Osler ME, HolmstrΓΆm MH, Zierath JR (2008) Gain-of-function R225Q mutation in AMP-activated protein kinase gamma3 subunit increases mitochondrial biogenesis in glycolytic skeletal muscle. J. Biol. Chem. 283: 35724-25734. |
Garcia Roves PM, Osler ME, Holmstroem MH, Zierath JR (2008) J. Biol. Chem.
Abstract: AMP-activated protein kinase (AMPK) is a heterotrimeric complex, composed of a catalytic subunit (Ξ±) and two regulatory subunits (Ξ² and Ξ³), that works as a cellular energy sensor. The existence of multiple heterotrimeric complexes provides a molecular basis for the multiple roles of this highly conserved signaling system. The AMPKΞ³3 subunit is predominantly expressed in skeletal muscle, mostly in type II glycolytic fiber types. We determined whether the AMPKΞ³3 subunit has a role in signaling pathways that mediate mitochondrial biogenesis in skeletal muscle. We provide evidence that overexpression or ablation of the AMPKΞ³3 subunit does not appear to play a critical role in defining mitochondrial content in resting skeletal muscle. However, overexpression of a mutant form (R225Q) of the AMPKΞ³3 subunit (Tg-AMPKΞ³3225Q) increases mitochondrial biogenesis in glycolytic skeletal muscle. These adaptations are associated with an increase in expression of the co-activator PGC-1Ξ± and several transcription factors that regulate mitochondrial biogenesis, including NRF-1, NRF-2, and TFAM. Succinate dehydrogenase staining, a marker of the oxidative profile of individual fibers, was also increased in transversal skeletal muscle sections of white gastrocnemius muscle from Tg-AMPKΞ³3225Q mice, independent of changes in fiber type composition. In conclusion, a single nucleotide mutation (R225Q) in the AMPK gamma3 subunit is associated with mitochondrial biogenesis in glycolytic skeletal muscle, concomitant with increased expression of the co-activator PGC-1Ξ± and several transcription factors that regulate mitochondrial proteins, without altering fiber type composition.
Labels:
Stress:Genetic Defect; Knockdown; Overexpression"Genetic Defect; Knockdown; Overexpression" is not in the list (Cell death, Cryopreservation, Ischemia-reperfusion, Permeability transition, Oxidative stress;RONS, Temperature, Hypoxia, Mitochondrial disease) of allowed values for the "Stress" property.
Tissue;cell: Skeletal Muscle"Skeletal Muscle" is not in the list (Heart, Skeletal muscle, Nervous system, Liver, Kidney, Lung;gill, Islet cell;pancreas;thymus, Endothelial;epithelial;mesothelial cell, Blood cells, Fat, ...) of allowed values for the "Tissue and cell" property.
Regulation: Respiration; OXPHOS; ETS Capacity"Respiration; OXPHOS; ETS Capacity" is not in the list (Aerobic glycolysis, ADP, ATP, ATP production, AMP, Calcium, Coupling efficiency;uncoupling, Cyt c, Flux control, Inhibitor, ...) of allowed values for the "Respiration and regulation" property., Mitochondrial Biogenesis; Mitochondrial Density"Mitochondrial Biogenesis; Mitochondrial Density" is not in the list (Aerobic glycolysis, ADP, ATP, ATP production, AMP, Calcium, Coupling efficiency;uncoupling, Cyt c, Flux control, Inhibitor, ...) of allowed values for the "Respiration and regulation" property.
HRR: Oxygraph-2k
