Intertissue regulation of carnitine palmitoyltransferase I (CPTI): Mitochondrial membrane properties and gene expression in rainbow trout (Oncorhynchus mykiss)

Carnitine palmitoyltransferase (CPT) I is regulated by several genetic and non-genetic factors including allosteric inhibition, mitochondrial membrane composition and/or fluidity and transcriptional regulation of enzyme content. To determine the intrinsic differences in these regulating factors that may result in differences between tissues in fatty acid oxidation ability, mitochondria were isolated from red, white and heart muscles and liver tissue from rainbow trout. Maximal activity (V_max) for β-oxidation enzymes and citrate synthase per mg tissue protein as well as CPT I in isolated mitochondria followed a pattern across tissues of red muscle > heart > white muscle > liver suggesting both quantitative and qualitative differences in mitochondria. CPT I inhibition showed a similar pattern with the highest malonyl-CoA concentration to inhibit activity by 50% (IC₅₀) found in red muscle while liver had the lowest. Tissue malonyl-CoA content was highest in white muscle with no differences between the other tissues. Interestingly, the gene expression profiles did not follow the same pattern as the tissue enzyme activity. CPT I mRNA expression was greatest in heart > red muscle > white muscle > liver. In contrast, PPARα mRNA was greatest in the liver > red muscle > heart > white muscle. There were no significant differences in the mRNA expression of PPARβ between tissues. As well, no significant differences were found in the mitochondrial membrane composition between tissues, however, there was a tendency for red muscle to exhibit higher proportions of PUFAs as well as a decreased PC:PE ratio, both of which would indicate increased membrane fluidity. In fact, there were significant correlations between IC₅₀ of CPT I for malonyl-CoA and indicators of membrane fluidity across tissues. This supports the notion that sensitivity of CPT I to its allosteric regulator could be modulated by changes in mitochondrial membrane composition and/or fluidity.