ATP Synthesis:- The Proton-Motive Force Energizes Active Transport
Although the primary role of the proton gradient in mitochondria is to furnish energy for the synthesis of ATP, the proton-motive force also drives several transport processes essential to oxidative phosphorylation. The inner mitochondrial membrane is generally impermeable to charged species, but two specific systems trans port ADP and Pi into the matrix and ATP out to the cy tosol (Fig. 19–26). The adenine nucleotide translocase, integral to the inner membrane, binds ADP3- in the intermembrane space and transports it into the matrix in exchange for an ATP4- molecule simultaneously transported outward (see Fig. 13–1 for the ionic forms of ATP and ADP). Because this antiporter moves four negative charges out for every three moved in, its activity is favored by the transmembrane electrochemical gradient, which gives the matrix a net negative charge; the proton-motive force drives ATP-ADP exchange. Adenine nucleotide translocase is specifically inhibited by atractyloside, a toxic glycoside formed by a species of thistle. If the transport of ADP into and ATP out of mitochondria is inhibited, cytosolic ATP cannot be regenerated from ADP, explaining the toxicity of atractyloside. A second membrane transport system essential to oxidative phosphorylation is the phosphate translocase, which promotes symport of one H2PO-4 and one H+ into the matrix. This transport process, too, is favored by the transmembrane proton gradient (Fig. 19–26). Notice that the process requires movement of one proton from the P to the N side of the inner mem brane, consuming some of the energy of electron trans fer. A complex of the ATP synthase and both translocases, the ATP synthasome, can be isolated from mitochondria by gentle dissection with detergents, suggesting that the functions of these three proteins are very tightly integrated.
FIGURE 19–26 Adenine nucleotide and phosphate translocases. Transport systems of the inner mitochondrial membrane carry ADP and Pi into the matrix and newly synthesized ATP into the cytosol. The adenine nucleotide translocase is an antiporter; the same protein moves ADP into the matrix and ATP out. The effect of replacing ATP4- with ADP3- is the net efflux of one negative charge, which is favored by the charge difference across the inner membrane (outside positive). At pH 7, Pi is present as both HPO4-2 and H2PO-4; the phosphate translocase is specific for H2PO-4. There is no net flow of charge during symport of H2PO-4 and H+, but the relatively low proton con centration in the matrix favors the inward movement of H+. Thus, the proton-motive force is responsible both for providing the energy for ATP synthesis and for transporting substrates (ADP and Pi) in and product (ATP) out of the mitochondrial matrix. All three of these transport systems can be isolated as a single membrane-bound complex (ATP synthasome).
