Garcia-Roves 2008 J Biol Chem
|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.
Abstract: AMP-activated protein kinase (AMPK) is a heterotrimeric complex, composed of a catalytic subunit (α) and two regulatory subunits (β and γ), 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 AMPKγ3 subunit is predominantly expressed in skeletal muscle, mostly in type II glycolytic fiber types. We determined whether the AMPKγ3 subunit has a role in signaling pathways that mediate mitochondrial biogenesis in skeletal muscle. We provide evidence that overexpression or ablation of the AMPKγ3 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 AMPKγ3 subunit (Tg-AMPKγ3225Q) increases mitochondrial biogenesis in glycolytic skeletal muscle. These adaptations are associated with an increase in expression of the co-activator PGC-1α 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-AMPKγ3225Q 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-1α and several transcription factors that regulate mitochondrial proteins, without altering fiber type composition. • Keywords: AMP-activated protein kinase (AMPK)
• 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