Pyruvate Oxidation and the Permeability of Mitochondria from Blowfly Flight Muscle

The rate of pyruvate oxidation by mitochondria from blowfly flight muscle decreased in the presence of tris (hydroxymethyl) aminomethane (Tris). An increase in the rate of mitochondrial swelling was concomitant with the loss of pyruvate oxidation. These changes were prevented by bovine serum albumin, adenosine triphosphate, and magnesium ions, factors required for mitochondrial contraction. Proline, but not glutamate or malate, restored the rate of pyruvate oxidation to original values. These findings suggest that mitochondrial swelling leads to leakage of intramitochondrial intermediates of the Krebs cycle, accounting for the decrease in the rate of pyruvate oxidation. Exogenous proline penetrates the mitochondrial membrane and is rapidly oxidized, via glutamate, forming intramitochondrial precursors of oxaloacetate. Malate and glutamate were ineffective because of the selective permeability of the mitochondrial membrane.