Direct manipulation of genes involved in mitochondrial content and metabolism modulates muscle Pi → ATP flux. Mice with muscle-specific overexpression of PGC1α (mPGC1α), a regulator of oxidative metabolism that increases
mitochondrial density and enhances expression and protein content of genes involved in oxidative phosphorylation, exhibit
a concomitant increase in Pi → ATP flux compared with wild-type (WT) mice. Muscle Pi → ATP flux is decreased in transgenic mice that overexpress UCP3 (UCP3-TG, D.E.B. and G.I.S unpublished observations), a
mitochondrial membrane protein found in skeletal muscle that may uncouple the H+ electrochemical gradient across the inner mitochondrial membrane and decrease the efficiency of oxidative phosphorylation.
Data obtained from UCP3-TG mice were acquired using the same experimental protocols described in Choi et al. (22). Data adapted from Choi et al. (22), reproduced courtesy of the National Academy of Sciences.