Origins of interspecies variation in mammalian muscle metabolic enzymes

• DOI: 10.1152/physiolgenomics.00025.2011
• Publication Date: 2011-05-18T00:24:12Z
• Authors: K. M. Kocha; C. E. Genge; C. D. Moyes
• Keywords: NRF1; Allometry

Do the transcriptional mechanisms that control an individual's mitochondrial content, PGC1α (peroxisome proliferator-activated receptor γ coactivator-1α) and NRF1 (nuclear respiratory factor-1), also cause differences between species? We explored determinants of cytochrome c oxidase (COX) activities in muscles from 12 rodents differing 1,000-fold mass. Hindlimb differed scaling patterns isometric (soleus, gastrocnemius) to allometric (tibialis anterior, coefficient = -0.16). Consideration myonuclear domain reduced within species, but interspecies remained. For tibialis there was no significant relationship mRNA/g for COX4-1, PGC1α, or NRF1, yet COX4-1 a good predictor COX activity (r(2) 0.55), mRNA correlated with each other 0.42), both could predict 0.48 0.52) 0.55 0.49). This paradox resolved by multivariate analysis, which explained 90% variation, about equally partitioned mass effects (or NRF1) levels, independent To explore mRNA, we analyzed 52 mammalian proximal promoters found size dependence regulatory element distribution. Likewise, promoter reporter genes 30 mammals showed body Collectively, these studies suggest not all scale equivalently, those show scaling, regulation master regulators, does account patterns, though it contribute