Garcia-Roves 2008 J Biol Chem

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Garcia-Roves PM, Osler ME, Holmstroem 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 283:35724-34.

Β» PMID: 18838377 Open Access

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. β€’ Keywords: AMP-activated protein kinase (AMPK)

β€’ O2k-Network Lab: ES Barcelona Garcia-Roves PM


Labels: MiParea: Respiration, mt-Biogenesis;mt-density, Genetic knockout;overexpression, Comparative MiP;environmental MiP 


Tissue;cell: Skeletal muscle  Preparation: Permeabilized tissue 


Coupling state: OXPHOS 

HRR: Oxygraph-2k 


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