Oxygen is the molecule that gets reduced in oxidative phosphorylation. Specifically, molecular oxygen (O₂) accepts electrons at the end of the electron transport chain and combines with protons to form water. This single reaction is the reason you breathe: your cells need a constant supply of oxygen to act as the final destination for electrons stripped from the food you eat.
Why Oxygen Is the Final Electron Acceptor
During oxidative phosphorylation, electrons are passed along a series of protein complexes embedded in the inner mitochondrial membrane. These electrons carry energy, and as they move from one complex to the next, that energy is used to pump protons across the membrane. At the very end of this chain, the electrons need somewhere to go. Oxygen serves as that terminal destination because it has a strong tendency to accept electrons, measured by what chemists call a high reduction potential (+820 millivolts). For comparison, the electron donors that start the chain (like the carrier molecule NADH) sit at about -320 millivolts. That enormous gap of over 1,100 millivolts is what drives the entire process forward.
The actual reduction happens at Complex IV, also called cytochrome c oxidase. Here, four electrons combine with one oxygen molecule and four protons to produce two molecules of water. The energy released in this final transfer is substantial: about 25.8 kilocalories per mole for the last step alone. Complex IV uses metal centers containing iron and copper to carefully control this reaction, ensuring oxygen is fully reduced to water rather than partially reduced into something harmful.
Other Molecules Reduced Along the Way
While oxygen is the big answer to “what is reduced,” it’s not the only molecule that undergoes reduction during the process. Several electron carriers get reduced and then re-oxidized as they shuttle electrons between complexes.
- Ubiquinone (Coenzyme Q) picks up two electrons and two protons to become ubiquinol, its reduced form. It acts as a mobile carrier, ferrying electrons from Complexes I and II to Complex III. The reduction happens in two steps, passing through an intermediate radical form along the way.
- Cytochrome c is a small protein on the outer face of the inner membrane. Complex III reduces it by handing off electrons, and then it carries those electrons to Complex IV, where it gets oxidized again. This constant cycling between reduced and oxidized states is what keeps the chain moving.
These carriers aren’t the final answer to what’s reduced, though. They’re middlemen. Every electron they accept is ultimately passed to oxygen.
How This Reduction Powers ATP Production
The reduction of oxygen doesn’t directly make ATP. Instead, it’s the engine that maintains the proton gradient across the inner mitochondrial membrane. As electrons flow through Complexes I, III, and IV, each complex pumps protons from inside the mitochondrial matrix to the space between the two mitochondrial membranes. This creates an electrical potential of roughly 150 to 180 millivolts across the inner membrane, a tiny but powerful voltage at the molecular scale.
Protons then flow back through ATP synthase, a rotating molecular turbine, and the energy of that flow drives the attachment of a phosphate group to ADP, creating ATP. For every pair of electrons donated by NADH, the cell produces approximately 2.5 ATP molecules. Electrons entering from a different carrier (FADH₂, which feeds into Complex II) generate about 1.5 ATP per pair, because they skip Complex I and pump fewer protons overall. These numbers account for the energy cost of transporting ATP out of the mitochondria and raw materials back in.
In total, oxidative phosphorylation generates 32 to 34 ATP molecules per glucose molecule, making it far more efficient than glycolysis alone.
What Happens When Oxygen Is Only Partially Reduced
The system isn’t perfect. Sometimes electrons leak from the chain before reaching Complex IV and land on oxygen prematurely, reducing it by just one electron instead of four. This produces superoxide, a reactive oxygen species (ROS) that can damage proteins, DNA, and cell membranes. Complexes I, II, and III all contain sites where this premature reduction can occur. Complex III is notable because it can release superoxide on both sides of the inner membrane, while Complexes I and II release it only into the matrix.
The partially reduced ubiquinone intermediate (called ubisemiquinone) at Complex III is a common culprit. Its unpaired electron can jump directly to a nearby oxygen molecule. Cells defend against this with enzymes called superoxide dismutases that convert superoxide into hydrogen peroxide, which is then neutralized by other protective systems. A low level of ROS production is normal and even plays a role in cell signaling, but excessive leakage is linked to aging and disease.
Anaerobic Alternatives to Oxygen
Some organisms run oxidative phosphorylation without oxygen by substituting a different molecule as the final electron acceptor. Certain bacteria can reduce nitrate, sulfate, iron, manganese dioxide, or even uranium instead of oxygen. The basic logic is the same: electrons flow through a chain of carriers, protons get pumped, and ATP synthase harvests the gradient. But these alternative acceptors have lower reduction potentials than oxygen, meaning less energy is released per electron transferred and fewer ATP molecules are produced. This is why aerobic respiration dominates in environments where oxygen is available. It simply extracts more energy from the same fuel.