Electron Transport in Mitochondria

The cells of almost all eukaryotes contain intracellular organelles called mitochondria, which produce ATP. Energy sources such as glucose are initially metabolized in the cytoplasm. The products are imported into mitochondria. Mitochondria continue the process of catabolism using metabolic pathways including the Krebs cycle, fatty acid oxidation, and amino acid oxidation.

The end result of these pathways is the production of two kinds of energy-rich electron donors, NADH and succinate. Electrons from these donors are passed through an electron transport chain to oxygen, which is reduced to water. This is a multi-step redox process that occurs on the mitochondrial inner membrane. The enzymes that catalyze these reactions have the ability to simultaneously create a proton gradient across the membrane, producing a thermodynamically unlikely high-energy state with the potential to do work. Although electron transport occurs with great efficiency, a small percentage of electrons are prematurely leaked to oxygen, resulting in the formation of the toxic free-radical superoxide.

The similarity between intracellular mitochondria and free-living bacteria is striking. The known structural, functional, and DNA similarities between mitochondria and bacteria provide strong evidence that mitochondria evolved from intracellular bacterial symbionts

Four membrane-bound complexes have been identified in mitochondria. Each is an extremely complex transmembrane structure that is embedded in the inner membrane. Three of them are proton pumps. The structures are electrically connected by lipid-soluble electron carriers and water-soluble electron carriers.

Complex I

Complex I (NADH dehydrogenase, also called NADH:ubiquinone oxidoreductase; EC removes two electrons from NADH and transfers them to a lipid-soluble carrier, ubiquinone (Q). The reduced product, ubiquinol (QH2) is free to diffuse within the membrane. At the same time, Complex I moves four protons (H+) across the membrane, producing a proton gradient. Complex I is one of the main sites at which premature electron leakage to oxygen occurs, thus being one of main sites of production of a harmful free radical called superoxide.

The pathway of electrons occurs as follows:

NADH is oxidized to NAD+, reducing Flavin mononucleotide to FMNH2 in one two-electron step. The next electron carrier is a Fe-S cluster, which can only accept one electron at a time to reduce the ferric ion into a ferrous ion. In a convenient manner, FMNH2 can be oxidized in only two one-electron steps, through a semiquinone intermediate. The electron thus travels from the FMNH2 to the Fe-S cluster, then from the Fe-S cluster to the oxidized Q to give the free-radical (semiquinone) form of Q. This happens again to reduce the semiquinone form to the ubiquinol form, QH2. During this process, four protons are translocated across the inner mitochondrial membrane, from the matrix to the intermembrane space. This creates a proton gradient that will be later used to generate ATP through oxidative phosphorylation.

Complex II

Complex II (succinate dehydrogenase; EC is not a proton pump. It serves to funnel additional electrons into the quinone pool (Q) by removing electrons from succinate and transferring them (via FAD) to Q. Complex II consists of four protein subunits: SDHA,SDHB,SDHC, and SDHD. Other electron donors (e.g., fatty acids and glycerol 3-phosphate) also funnel electrons into Q (via FAD), again without producing a proton gradient.

Complex III

Complex III (cytochrome bc1 complex; EC removes in a stepwise fashion two electrons from QH2 at the QO site and sequentially transfers them to two molecules of cytochrome c, a water-soluble electron carrier located within the intermembrane space. The two other electrons are sequentially passed across the protein to the Qi site where quinone part of ubiquinone is reduced to quinol. A proton gradient is formed because it takes 2 quinol (4H+4e-) oxidations at the Qo site to form one quinol (2H+2e-) at the Qi site. (in total 6 protons: 2 protons reduce quinone to quinol and 4 protons are released from 2 ubiquinol). The bc1 complex does NOT 'pump' protons, it helps build the proton gradient by an asymmetric absorption/release of protons.

When electron transfer is hindered (by a high membrane potential, point mutations or respiratory inhibitors such as antimycin A), Complex III may leak electrons to oxygen resulting in the formation of superoxide, a highly-toxic species, which is thought to contribute to the pathology of a number of diseases, including aging.

Complex IV

Complex IV (cytochrome c oxidase; EC removes four electrons from four molecules of cytochrome c and transfers them to molecular oxygen (O2), producing two molecules of water (H2O). At the same time, it moves four protons across the membrane, producing a proton gradient.

Coupling with oxidative phosphorylation

The chemiosmotic coupling hypothesis, as proposed by Nobel Prize in Chemistry winner Peter D. Mitchell, explains that the electron transport chain and oxidative phosphorylation are coupled by a proton gradient across the inner mitochondrial membrane. The efflux of protons creates both a pH gradient and an electrochemical gradient. This proton gradient is used by the FOF1 ATP synthase complex to make ATP via oxidative phosphorylation. ATP synthase is sometimes regarded as complex V of the electron transport chain. The FO component of ATP synthase acts as an ion channel for return of protons back to mitochondrial matrix. During their return, the free energy produced during the generation of the oxidized forms of the electron carriers (NAD+ and Q) is released. This energy is used to drive ATP synthesis, catalyzed by the F1 component of the complex.
Coupling with oxidative phosphorylation is a key step for ATP production. However, in certain cases, uncoupling may be biologically useful. The inner mitochondrial membrane of brown adipose tissue contains a large amount of thermogenin (an uncoupling protein), which acts as uncoupler by forming an alternative pathway for the flow of protons back to matrix. This results in consumption of energy in thermogenesis rather than ATP production. This may be useful in cases when heat production is required, for example in colds or during arise of hibernating animals. Synthetic uncouplers (e.g., 2,4-dinitrophenol) also exist, and, at high doses, are lethal.


The mitochondrial electron transport chain removes electrons from an electron donor (NADH or QH2) and passes them to a terminal electron acceptor (O2) via a series of redox reactions. These reactions are coupled to the creation of a proton gradient across the mitochondrial inner membrane. There are three proton pumps: I, III, and IV. The resulting transmembrane proton gradient is used to make ATP via ATP synthase.

The reactions catalyzed by Complex I and Complex III exist roughly at equilibrium. This means that these reactions are readily reversible, simply by increasing the concentration of the products relative to the concentration of the reactants (for example, by increasing the proton gradient). ATP synthase is also readily reversible. Thus ATP can be used to make a proton gradient, which in turn can be used to make NADH. This process of reverse electron transport is important in many prokaryotic electron transport chains.

Electron transport chain. (2009, September 7). In Wikipedia, The Free Encyclopedia. Retrieved 21:19, September 7, 2009, from http://en.wikipedia.org/w/index.php?title=Electron_transport_chain&oldid=312464432

No comments:
Write comments
Recommended Posts × +