Fundamentals of Molecular Biology. Part 1: Molecular Cell Biology - A. N. Ogurtsov 2011

Generation of the proton-motive force and ATP synthesis
Transport of ATP and ADP across the inner mitochondrial membrane

The proton-motive force not only serves as an energy source for ATP synthesis, but also drives the Transport Across the inner membrane of those ATP molecules synthesized within the mitochondrial matrix during Oxidative Phosphorylation in exchange for ADP and Pi from the intermembrane space. This exchange, which is essential for sustaining oxidative phosphorylation continuously, is mediated by two transport Proteins located in The inner mitochondrial membrane (Figure 173):

1) the phosphate carrier (HPO42-/OH- antiporter),

2) the ATP/ADP antiporter.

The phosphate carrier couples the translocation of one HPO42- ion into the matrix with the export of one hydroxyl ion (OH-) out of the mitochondrial matrix. Similarly, the ATP/ADP antiporter translocates one ADP molecule into the matrix simultaneously with the export of one ATP molecule out of the matrix. Comprising 10–15% of the inner mitochondrial Membrane Proteins, ATP/ADP antiporters are the most abundant mitochondrial proteins.

The pumped-out hydroxyl ions (OH-) combine with protons (H+) that are extruded from the matrix by The electron transport systems, resulting in The formation of Water molecules (H2O). This water formation maintains the proton and hydroxyl ion gradients at a level that ensures the continuous operation of the transport antiporters.

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Figure 173 - Transport systems for ATP, ADP, and Pi in the inner mitochondrial membrane

Those protons that were previously pumped out of the matrix during electron transfer and subsequently consumed in recombination with hydroxyl ions to support the Transmembrane Transport of ATP, ADP, and Pi do not, obviously, participate in the proton current driving ATP synthases.

It is estimated that of the four translocated protons, three are used for ATP synthesis, while the fourth is expended on exporting this ATP molecule through the coordinated action of the two transport antiporters.

As a result, The Cell Cytosol achieves both a high ATP concentration—which is subsequently utilized in various energy-dependent cellular processes—and the concentrations of ADP and Pi in the mitochondrial matrix required for continuous ATP synthesis.

The Role of ADP concentration. If an isolated mitochondrion is supplied with adequate amounts of NADH, O2, and Pi, but is deprived of ADP molecules, The oxidation of NADH and the reduction of O2 will rapidly cease because the ADP pool is quickly depleted through ATP synthesis. However, if ADP is subsequently added to the system, NADH oxidation resumes. Consequently, a mitochondrion can oxidize FADH2 and NADH only when a source is available to replenish the pool of ADP and Pi required for ATP synthesis.

This phenomenon, known as Respiratory Control (or respiratory regulation), occurs because the oxidation of NADH, succinate, or FADH2 is obligatorily coupled to proton transport across the inner mitochondrial membrane.

If the generated proton-motive force is not consumed in the synthesis of ATP from ADP and Pi (or for any other reason), both the transmembrane proton gradient and the Membrane Potential rise to very high values. In this case, continuing proton translocation would demand such high Energy Expenditure that the process inevitably slows down, blocking the coupled oxidation of NADH and other metabolites.

Self-Control Questions

1. What fraction of the Free energy released during the Complete oxidation of glucose is conserved in the Coenzymes NADH and FADH2?

2. What process is termed oxidative phosphorylation?

3. Which multi-Structure/178.html">Protein Complexes make up the Respiratory Chain?

4. The oxidation of which coenzymes serves as the energy source for generating the proton-motive force across the inner mitochondrial membrane?

5. Which electron acceptors are utilized in the respiratory chain?

6. How does The structure of cytochrome heme groups allow for the determination of a given cytochrome's reduction potential?

7. Which electron carriers are employed in the respiratory chain?

8. What are the Similarities and differences between the mobile electron carriers ubiquinone and cytochrome c?

9. What are the Specific features of Complex I of the respiratory chain?

10. What are the specific features of Complex II of the respiratory chain?

11. What are the specific features of Complex III of the respiratory chain?

12. What is the specific feature of complex IV of the respiratory chain?

13. How many protons are translocated in total across the inner mitochondrial membrane per pair of electrons passing down the respiratory chain from NADH to O2?

14. What is the biological function of the multienzyme F0F1 complex?

15. Which subunits comprise the membrane-embedded F0 component?

16. Which subunits make up the cytosolic F1 component?

17. How does the transmembrane proton flux through the F0 complex drive ATP Synthesis in the F1 complex?

18. Which membrane systems ensure the continuity of oxidative phosphorylation? What force serves as the energy source for this process?

19. What is respiratory control?

20. How does respiratory control coordinate oxidation and phosphorylation processes within the mitochondrion?



Last update: 12/08/2026

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