Figure 1.

Increased flux through β-oxidation increases JO₂, JH₂O₂ production, and electron flux through redox buffering circuits. A, schematic showing the mechanism by which carnitine via CrAT relieves acetyl-CoA–mediated inhibition of β-oxidation (left), sites of H₂O₂ generation from β-oxidation dehydrogenases (blue type, center), and the thioredoxin (Trx) and GSH redox buffering circuits (right). B, JH₂O₂ (left y axis) measured in mitochondria isolated from mouse skeletal muscle supported by PCoA (10 μm) and either low (25 μm) or high (5 mm) carnitine followed by the addition of AF/BCNU (1 μm/100 μm), inhibitors of Trx and GSH reductases, respectively. The percentage of JH₂O₂ buffered (right of dotted line, right y axis) reflects the percentage of JH₂O₂ produced but not emitted (i.e. (JH₂O₂ production (AF/BCNU rate) – JH₂O₂ emission (PCoA + carnitine rate))/JH₂O₂ production × 100). C, JO₂ measured in mitochondria isolated from mouse skeletal muscle during basal (no ADP) respiration supported by PCoA (10 μm) and increasing concentrations of carnitine. D, PCoA plus carnitine (5 mm) supported JO₂ during basal (state 4) or ADP-stimulated (state 3) respiration in the absence or presence of malonyl-CoA (100 μm), a CPT-1 inhibitor. E, JO₂ measured in PmFBs from WT and CrAT^m/− mice during respiration supported by palmitoyl-carnitine (20 μm) followed by the additions of carnitine (5 mm) and malate (0.2 mm). All data are means ± S.E. (error bars); *, p < 0.05 versus corresponding control by unpaired t test; n = 5–13 mice/group.