By Christopher Robison Updated Aug 30, 2022

The electron transport chain (ETC) is the powerhouse of aerobic cells, driving the majority of ATP synthesis through a series of tightly coupled redox reactions. As electrons move along the mitochondrial inner membrane, protons are pumped into the intermembrane space, establishing a proton motive force (PMF). The PMF then powers ATP synthase, converting ADP and inorganic phosphate into the universal energy currency of the cell.

The Citric Acid Cycle Feeds the ETC

Central to the ETC are the electron donors succinate and nicotinamide adenine dinucleotide (NADH). These are produced during the citric acid cycle (CAC), the metabolic hub that oxidizes carbohydrates, fats, and proteins into pyruvate and acetyl‑CoA. Each turn of the CAC generates six NADH molecules and one succinate, directly linking metabolic flux to electron supply for the ETC.

NADH and FADH₂

Within the mitochondrial matrix, NAD⁺ accepts a proton and two electrons to form NADH. The matrix-localized Complex I (NADH dehydrogenase) transfers these electrons to ubiquinone, concurrently pumping four protons across the membrane and reinforcing the PMF. A parallel pathway involves flavin adenine dinucleotide (FADH₂), which donates electrons to Complex II (succinate dehydrogenase) without proton pumping, yet still feeds electrons into the chain.

Succinate and QH₂

During the CAC, succinate is oxidized to fumarate, generating FADH₂ that reduces ubiquinone to ubiquinol (QH₂). QH₂ then powers Complex III (cytochrome bc1 complex), which pumps additional protons and passes electrons to Complex IV (cytochrome c oxidase). Complex IV completes the process by transferring electrons to oxygen, the chain’s terminal acceptor.

Oxygen as the Terminal Electron Acceptor

Oxygen is indispensable for efficient ATP production. It accepts electrons at Complex IV, becoming reduced to water and consuming protons in the process. In the absence of oxygen, cells resort to anaerobic pathways that yield far fewer ATP molecules.

ADP, Pi, and ATP Synthesis

The culmination of the ETC is the synthesis of ATP. The PMF drives protons back into the matrix through ATP synthase, with an estimated 3.5 protons required per ATP formed. ADP and inorganic phosphate (Pi) are imported into the matrix, and the energy from the proton flow drives their phosphorylation, producing ATP that fuels virtually all cellular processes.