Allometric Scaling Of Muscle Metabolic Enzymes in Mammals

Abstract

Are the transcriptional mechanisms that control mitochondrial content in an individual ‐NRF1 and PGC1alpha (PGC1)‐ also responsible for interspecies differences? We explored the origins of allometric scaling of cytochrome oxidase (COX) activities in muscles from 12 rodents differing 1000‐fold in mass. Muscle COX scaling patterns ranged from isometric (soleus) to allometric (tibialis anterior). Consideration of myonuclear domain reduced differences between muscles, but not interspecies differences. In tibialis anterior, there was no significant scaling relationship in mRNA/g for COX4‐1, PGC1 or NRF1 yet COX4‐1 mRNA/g predicted COX activity, PGC1 and NRF1 mRNA correlated with each other, and both predicted COX4‐1 mRNA and COX activity. Multivariate analysis explained 90% of COX variation between species, about equally partitioned between mass effects and mass‐independent effects on PGC1 (or NRF1) mRNA. In mammalian PGC1 proximal promoters, there were no mass‐linked differences in (i) distribution of regulatory elements or (ii) reporter gene activities. Collectively, these studies suggest that not all muscles scale equivalently, but for those that show allometric scaling, transcriptional regulation of PGC1 and NRF1 genes does not account for scaling patterns, though it does explain most of the mass‐independent differences between species. Funded by NSERC Canada.