Electrons flow through the electron transport chain to molecular oxygen; during this flow, protons are moved across the inner membrane from the matrix to the intermembrane space. This model for ATP synthesis is called the chemiosmotic mechanism, or Mitchell hypothesis. Peter Mitchell, a British biochemist, essentially by himself and in the face of contrary opinion, proposed that the mechanism for ATP synthesis involved the coupling between chemical energy (ATP) and osmotic potential (a higher concentration of protons in the intermembrane space than in the matrix). The inner membrane of the mitochondrion is tightly packed with cytochromes and proteins capable of undergoing redox changes. There are four major protein‐membrane complexes.
Complex I and Complex II
Complex I and Complex II direct electrons to coenzyme Q. Complex I, also called NADH‐coenzyme Q reductase, accepts electrons from NADH. The NADH releases a proton and two electrons. The electrons flow through a flavoprotein containing FMN and an iron‐sulfur protein. First, the flavin coenzyme (flavin mononucleotide) and then the iron‐sulfur center undergo cycles of reduction and then oxidation, transferring their electrons to a quinone
molecule, coenzyme Q
(see Figure 1
). Complex I is capable of transferring protons from the matrix to the intermembrane space while undergoing these redox cycles. One possible source of the protons is the release of a proton from NADH as it is oxidized to NAD, although this is not the only explanation. Apparently, conformational changes in the proteins of Complex I also are involved in the mechanism of proton translocation during electron transport.
Complex II, also known as succinate‐coenzyme Q reductase, accepts electrons from succinate formed during the TCA cycle. Electrons flow from succinate to FAD (the flavin‐adenine dinucleotide) coenzyme, through an iron‐sulfur protein and a cytochrome b 550 protein (the number refers to the wavelength where the protein absorbs), and to coenzyme Q. No protons are translocated by Complex II. Because translocated protons are the source of the energy for ATP synthesis, this means that the oxidation of a molecule of FADH 2 inherently leads to less ATP synthesized than does the oxidation of a molecule of NADH. This experimental observation also fits with the difference in the standard reduction potentials of the two molecules. The reduction potential of FAD is ‐0.22 V, as opposed to ‐0.32 V for NAD.
Coenzyme Q is capable of accepting either one or two electrons to form either a semiquinone or hydroquinone form. Figure 2 shows the quinone, semiquinone, and hydroquinone forms of the coenzyme. Coenzyme Q is not bound to a protein; instead it is a mobile electron carrier and can float within the inner membrane, where it can transfer electrons from Complex I and Complex II to Complex III.
Complex III is also known as coenzyme Q‐cytochrome c reductase. It accepts electrons from reduced coenzyme Q, moves them within the complex through two cytochromes b, an iron‐sulfur protein, and cytochrome c 1. Electron flow through Complex II transfers proton(s) through the membrane into the intermembrane space. Again, this supplies energy for ATP synthesis. Complex III transfers its electrons to the heme group of a small, mobile electron transport protein, cytochrome c.
Cytochrome c transfers its electrons to the final electron transport component, Complex IV, or cytochrome oxidase. Cytochrome oxidase transfers electrons through a copper‐containing protein, cytochrome a, and cytochrome a 3, and finally to molecular oxygen. The overall pathway for electron transport is therefore:
The number n is a fudge factor to account for the fact that the exact stoichiometry of proton transfer isn't really known. The important point is that more proton transfer occurs from NADH oxidation than from FADH 2 oxidation.