The Electron Transport Chain (ETC) is the final, most productive stage of cellular respiration, converting nutrients into usable energy. This series of protein complexes is situated within the inner membrane of the mitochondrion. The ETC harnesses the energy released by electron movement to create a concentration difference of protons (hydrogen ions) across this membrane. This electrochemical gradient ultimately powers the synthesis of adenosine triphosphate (ATP), the primary energy currency fueling cellular activities.
Initial Electron Capture (Complexes I and II)
The process begins with the delivery of high-energy electrons from carrier molecules, such as Nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (\(\text{FADH}_2\)), generated during earlier metabolic stages. These molecules act as primary electron donors, initiating two distinct entry points into the chain. The first entry point is Complex I, also known as NADH dehydrogenase, a large protein structure embedded in the inner membrane.
Complex I accepts two high-energy electrons from NADH, oxidizing it back to \(\text{NAD}^+\). As these electrons move through internal iron-sulfur clusters, the released energy powers a molecular pump. This action forces four protons from the mitochondrial matrix into the intermembrane space, contributing to the proton gradient. The electrons are then passed to a mobile, lipid-soluble carrier called Coenzyme Q (Q).
A separate entry point is Complex II, or succinate dehydrogenase, which is unique as the only enzyme involved in both the Krebs cycle and the ETC. Complex II is not a proton pump because the electrons it receives are at a lower energy level than those from NADH. This complex accepts electrons from \(\text{FADH}_2\), oxidizing it back to \(\text{FAD}\) and transferring the electrons through its iron-sulfur centers.
The electrons from Complex II are also transferred to the mobile carrier Coenzyme Q. Since \(\text{FADH}_2\) bypasses Complex I, its electrons enter the chain later, resulting in a lower energy yield and fewer protons pumped compared to NADH. Once Coenzyme Q accepts electrons, it is reduced to ubiquinol (\(\text{QH}_2\)), which diffuses through the membrane to the next complex.
Establishing the Proton Gradient (Complexes III and IV)
The reduced ubiquinol (\(\text{QH}_2\)) carries the collected electrons to Complex III, or cytochrome c reductase, which performs the Q-cycle. This complex uses a two-step mechanism to separate the two electrons carried by ubiquinol, transferring them one at a time to the next mobile carrier, Cytochrome c. The Q-cycle is an electron-recycling loop that maximizes the energy harvest from ubiquinol.
Complex III oxidizes two \(\text{QH}_2\) molecules, resulting in the reduction of two Cytochrome c molecules. This process is coupled to the pumping of four protons from the matrix into the intermembrane space, boosting the electrochemical gradient. The small, water-soluble protein Cytochrome c, which carries a single electron, then shuttles along the inner membrane surface to deliver its electron to the final major protein complex.
Cytochrome c delivers its electron to Complex IV, or cytochrome c oxidase, the final destination for electrons within the ETC. This complex is responsible for the terminal reaction of aerobic respiration: safely reducing molecular oxygen. Complex IV must receive four electrons (one from each of four Cytochrome c molecules) to reduce a single molecule of oxygen (\(\text{O}_2\)) to two molecules of water (\(\text{H}_2\text{O}\)).
The reduction of oxygen is controlled by copper and heme iron centers to prevent the formation of free radicals. The energy released during this final transfer is used to pump four additional protons across the membrane for every \(\text{O}_2\) molecule reduced. This action depletes the electrons’ energy and establishes the proton concentration difference, representing a store of potential energy ready for harvesting.
Harvesting Energy (ATP Synthase)
The sequential pumping action of Complexes I, III, and IV creates a high concentration of protons in the intermembrane space, forming an electrochemical potential difference across the inner mitochondrial membrane. This stored energy, called the proton-motive force, drives protons to flow back into the matrix. The conversion of this potential energy into chemical energy is called chemiosmosis, carried out by the final enzyme, Complex V, or ATP Synthase.
ATP Synthase functions like a rotary turbine spanning the inner mitochondrial membrane. The enzyme has two main parts: the \(\text{F}_O\) unit, embedded in the membrane, which acts as the proton channel and motor; and the \(\text{F}_1\) unit, which extends into the matrix and is the site of ATP synthesis. Protons move down their concentration gradient, flowing through the \(\text{F}_O\) channel and causing a central rotor shaft to spin.
The mechanical rotation of the central stalk transmits energy to the \(\text{F}_1\) unit, which contains the catalytic sites for ATP production. This rotation forces conformational changes in the \(\text{F}_1\) subunits, cycling them through three distinct states: binding ADP and inorganic phosphate (\(\text{P}_i\)), catalyzing bond formation to create ATP, and releasing the synthesized ATP molecule. The energy from the proton flow is directly coupled to this mechanical rotation, which drives the phosphorylation of ADP to produce ATP.