Question

The electron transport chain has two diffusible electron carriers, ubiquinone, which shuttles electrons to the third mitochondrial complex, and cytochrome c, which shuttles electrons to the last mitochondrial complex (see figure below). Would it be possible for cells to use only one of these two diffusible electron carriers to shuttle electrons at each of these two steps of the electron transport chain? Why or why not?

Answer 1

1. An electron from NADH is first accepted by the protein complex NADH-Q reductase, also known as the NADH dehydrogenase complex. This is the largest of the electron carriers, consisting of more than 22 protein chains. The NADH-Q reductase complex accepts an electron from NADH and passes the electron to the next electron carrier, ubiquinone, which has a higher reduction potential.

1. Ubiquinone, abbreviated as Q, is an organic molecule (not a protein) dissolved in the hydrophobic region of the inner membrane of the mitochondrion. It can move freely within the hydrophobic region of the membrane, by diffusion. [Note that ubiquinone diffuses from one region of the membrane to another (i.e.,within the walls of the membrane), whereas polar molecules can diffuse from one side of the membrane to the other side (i.e., across the membrane) through channels.]

Ubiquinone has a higher reduction potential than the NADH-Q reductase. Hence, when ubiquinone in the oxidized form comes in contact with the NADH-Q reductase complex (by a random collision), this mobile electron carrier accepts an electron from NADH-Q reductase (i.e., gets reduced). (Note: Because the electron-transport chain has mobile electron carriers, the electron-carriers need not be located next to each other. It is the difference in reduction potential, not spatial arrangement, that causes the electron to flow sequentially from one carrier to another.)

The free energy released by the spontaneous transfer of electrons from the NADH-Q reductase complex to ubiquinone is used for a very important purpose. , this free energy is used to pump protons (H+ ions) out of the matrix, through the NADH-Q reductase (which spans the membrane), and into the intermembrane space, building up a significant proton-concentration gradient. As we will see later, this proton gradient ultimately provides the energy needed to generate ATP! Hence NADH-Q reductase acts as both an electron carrier and a proton pump.Ubiquinone is an electron carrier only; it is not a proton pump.  Therefore, ubiquinone does not increase the H+ concentration in the intermembrane space.

1. The reduced form of ubiquinone then continues to move through the hydrophobic region of the membrane by diffusion. When the ubiquinone comes in contact with the next carrier in the electron-transport chain, the electron is transferred to this protein complex, known as cytochrome reductase, or the cytochrome b-c1 complex. This complex is actually a dimer, i.e., it consists of two membrane-spanning protein subunits. Electrons from ubiquinone are first accepted by the subunit called cytochrome b, which then passes the electron to the other protein subunit of cytochrome reductase, which is called cytochrome c1. As shown in Table 2, the cytochrome c1 subunit has a higher reduction potential than the cytochrome b subunit.

1. From cytochrome reductase, the electron is picked up by another mobile electron carrier, cytochrome c (not to be confused with the cytochrome c1 subunit of cytochrome reductase). Cytochrome c is a small protein containing one heme group. When the oxidized form of cytochrome c contacts the cytochrome reductase complex by a random collision, its heme group can accept an electron from the heme group of the cytochrome c1 subunit (in cytochrome reductase). Cytochrome c then carries this electron until the carrier collides with the final protein carrier in the electron-transport chain, cytochrome oxidase.

Like NADH-Q reductase, cytochrome reductase acts as both an electron carrier and a proton pump. As the electron is spontaneously transferred from one group to another in the protein complex, free energy is released. This free energy is used to pump protons from the matrix, across the inner mitochondrial membrane (through cytochrome reductase), and into the intermembrane space. Hence, the proton gradient is increased further.

1. Cytochrome oxidase is the best understood of all the electron-carrier proteins involved in oxidative phosphorylation. In many ways this protein is similar to NADH-Q reductase and cytochrome reductase, which are discussed above. Cytochrome oxidase accepts an electron from cytochrome c, and passes it to O2, the final electron acceptor in this chain. The mechanism for this final electron transfer is described in the yellow box, below. (It is interesting to note that azide, which is used in airbags, is toxic to us because it binds to cytochrome oxidase and blocks this important electron transfer.) As with the other proteins, the free energy from the spontaneous oxidation-reduction reaction is used to pump more protons into the intermembrane space, increasing the proton gradient even further.