Figure 3. Protein transporters regulate metabolic substrate entry into the mitochondrial matrix and control the relative rates of oxidative metabolism.

Fatty acyl CoA (FA-CoA) and pyruvate enter the mitochondria through protein transporters. FA-CoA is first converted to fatty acyl-carnitine (FA-carnitine) by carnitine palmitoyltransferase 1 (CPT1) located on the outer mitochondrial membrane (OMM). CPT1 activity is controlled by the concentration of malonyl CoA and therefore the activities of malonyl CoA decarboxylase (MCD) and acetyl CoA carboxylase 2 (ACC2) indirectly regulate CPT1 activity. FA-carnitine enters the mitochondria via carnitine-acylcarnitine translocase where it is then converted back to FA-CoA by CPT2 located on the inner mitochondrial membrane (IMM). FA-CoA is then able to undergo oxidation within the mitochondria to yield acetyl CoA for the citric acid cycle (CAC). Pyruvate enters the mitochondria via the newly discovered mitochondrial pyruvate carriers 1 and 2 (MPC1 and MPC2) protein complex. Pyruvate is then converted to acetyl CoA by the actions of pyruvate dehydrogenase (PDH). Acetyl CoA exerts product inhibition on the activity of PDH. CACT indicates carnitine-acylcarnitine translocase.