Principles of Biochemistry Volume 2 - A. Lehninger 1985

Bioenergetics and Metabolism
Electron Transport, Oxidative Phosphorylation, and Regulation of ATP Synthesis
The inner mitochondrial membrane contains specific transport systems

The inner mitochondrial membrane is impermeable not only to H⁺, OH^-, and K⁺ ions, but also to many other ionized solutes. How then do charged particles such as ADP^3- and phosphate^2-, generated in the Cytosol during ATP breakdown, enter the mitochondrial matrix, and how does newly synthesized ATP^4- (since Oxidative Phosphorylation occurs inside the Cell/35.html">Mitochondria) exit the matrix? The inner mitochondrial membrane contains two specific transport systems (Fig. 17-25) that make this possible. The first of these, the adenine nucleotide translocase, transports ADP^3- from the cytosol into the mitochondria, with one ADP^3- entering for each ATP^4- exiting. Adenine nucleotide translocase is a specific protein that spans the entire thickness of the inner mitochondrial membrane and binds ADP^3- at a strictly defined site on the outer surface of this membrane. The translocation of ADP^3- into the mitochondrion in exchange for exiting ATP^4- is driven by a conformational change in the adenine nucleotide translocase molecule. The adenine nucleotide translocase system is highly specific; it transports only ATP and ADP, but does not transport AMP or other NUCLEOTIDES, such as GDP or GTP.

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Fig. 17-24. Rotation of bacterial flagella driven by the "proton-motive force." Bacterial flagella are rigid structures distinct from corresponding eukaryotic appendages. Rotational movement is imparted to the flagella by a specialized Structure located in The Cell membrane, known as the "proton turbine." H⁺ ions, pumped outward As a result of electron transfer, flow back into the cell through this "turbine," driving flagellar rotation.

A highly specific inhibitor of the adenine nucleotide translocase has been discovered. This inhibitor is atractyloside, a toxic glycoside produced by a species of thistle found in certain Regions of the Mediterranean. Local inhabitants have known since ancient times that livestock can be poisoned by eating this plant at certain times of the year. The isolation of this factor in pure form and the elucidation of its role—specifically, its action as an inhibitor of adenine nucleotide translocation—was the result of a series of brilliant studies conducted by Italian, French, German, and American biochemists. Clearly, if adenine nucleotide transport is impaired in Cells so that ADP does not enter the mitochondria and ATP does not exit them, the regeneration of cytosolic ATP and ADP becomes impossible.

The second membrane transport system involved in oxidative phosphorylation transports the H₂PO₄^- ion from the cytosol into the mitochondria, accompanied by an H⁺ ion (Fig. 17-25).

Fig. 17-25. Transport systems of the inner mitochondrial membrane that move ADP and phosphate from the cytosol into the matrix, and newly synthesized ATP from the matrix into the cytosol.

This enzyme system, designated as phosphate translocase, is specific for phosphate and is likewise inhibited by certain chemical agents. Through the concerted action of phosphate translocase and adenine nucleotide translocase, phosphate and ADP are able to enter the mitochondrial matrix, while ATP exits the mitochondria into the cytosol, where the majority of energy-requiring cellular processes take place.

In Liver mitochondria, the inner membrane also contains specific transport systems. These include systems for The transport of Pyruvate, which enters the mitochondrial matrix from the cytosol where it is produced; dicarboxylates, such as malate and succinate; and tricarboxylates, such as citrate and isocitrate. Mitochondria also possess transport systems specific for aspartate and glutamate.