Origins of interspecies variation in mammalian muscle metabolic enzymes

Abstract

Kocha KM, Genge CE, Moyes CD. Origins of interspecies variation in mammalian muscle metabolic enzymes. Physiol Genomics 43: 873-883, 2011. First published May 17, 2011 doi:10.1152/physiolgenomics.00025.2011.-Do the transcriptional mechanisms that control an individual's mitochondrial content, PGC1␣ (peroxisome proliferator-activated receptor ␥ coactivator-1␣) and NRF1 (nuclear respiratory factor-1), also cause differences between species? We explored the determinants of cytochrome c oxidase (COX) activities in muscles from 12 rodents differing 1,000-fold in mass. Hindlimb muscles differed in scaling patterns from isometric (soleus, gastrocnemius) to allometric (tibialis anterior, scaling coefficient ϭ Ϫ0.16). Consideration of myonuclear domain reduced the differences within species, but interspecies differences remained. For tibialis anterior, there was no significant scaling relationship in mRNA/g for COX4-1, PGC1␣, or NRF1, yet COX4-1 mRNA/g was a good predictor of COX activity (r 2 ϭ 0.55), PGC1␣ and NRF1 mRNA correlated with each other (r 2 ϭ 0.42), and both could predict COX4-1 mRNA (r 2 ϭ 0.48 and 0.52) and COX activity (r 2 ϭ 0.55 and 0.49). This paradox was resolved by multivariate analysis, which explained 90% of interspecies variation, about equally partitioned between mass effects and PGC1␣ (or NRF1) mRNA levels, independent of mass. To explore the determinants of PGC1␣ mRNA, we analyzed 52 mammalian PGC1␣ proximal promoters and found no size dependence in regulatory element distribution. Likewise, the activity of PGC1␣ promoter reporter genes from 30 mammals showed no significant relationship with body mass. Collectively, these studies suggest that not all muscles scale equivalently, but for those that show allometric scaling, transcriptional regulation of the master regulators, PGC1␣ and NRF1, does not account for scaling patterns, though it does contribute to interspecies differences in COX activities independent of mass.scaling; cytochrome c oxidase; peroxisome proliferator-activated receptor ␥ coactivator-1␣; nuclear respiratory factor-1; mitochondria; lactate dehydrogenase ALL ANIMALS HAVE THE NEED to alter muscle mitochondrial content during development and in response to physiological and environmental challenges. Central to this remodeling process are transcriptional master regulators, namely peroxisome proliferator-activated receptor ␥ coactivator-1␣ (PGC1␣) and nuclear respiratory factor-1 (NRF1) (20,33,34). Mitochondrial biogenesis requires the coordination of hundreds of nuclear genes encoding mitochondrial structural and enzymatic proteins, including the proteins that control replication, transcription, and translation of mitochondrial DNA. This onerous task is mediated by the coactivator PGC1␣, which regulates suites of nuclear-encoded metabolic genes through direct and indirect association with DNA-binding transcription factors. Central to control of genes in oxidative phosphorylation are NRF1, NRF2, and nuclear hormone receptors [e.g., peroxisome proliferator-activated receptor (PPAR...

Transcriptional regulation of temperature-induced remodeling of muscle bioenergetics in goldfish

“…Preliminary Western blots were run with rodent samples to ensure that the antibodies (directed to mammalian epitopes) identified corresponding bands in both mammals and fish. Rodent samples were obtained from material archived from previous studies (29).…”