Electron Transport Chain (ETC)
The electron transport chain is a set of protein complexes in the inner mitochondrial membrane that makes most of the cell's ATP. It is the final stage of aerobic cellular respiration.
Main function
It transfers high-energy electrons from NADH and FADH₂ to oxygen (O₂). The energy released pumps protons (H⁺) from the mitochondrial matrix into the intermembrane space. This proton gradient then powers ATP production by ATP synthase.
The overall process is called
oxidative phosphorylation.
NCBI's ETC overview describes the chain as redox reactions coupled to creation of an electrochemical gradient for ATP synthesis.
Location
- Eukaryotic cells: inner mitochondrial membrane
- Prokaryotes: plasma membrane
Components and electron flow
| Component | Role |
|---|
| Complex I: NADH dehydrogenase | Receives electrons from NADH; pumps 4 H⁺ |
| Complex II: Succinate dehydrogenase | Receives electrons from FADH₂; does not pump H⁺ |
| Coenzyme Q (ubiquinone) | Mobile lipid-soluble carrier that carries electrons from I/II to III |
| Complex III: cytochrome bc₁ | Transfers electrons to cytochrome c; pumps 4 H⁺ |
| Cytochrome c | Small mobile protein carrier between III and IV |
| Complex IV: cytochrome c oxidase | Transfers electrons to O₂, producing H₂O; pumps 2 H⁺ |
| Complex V: ATP synthase | Uses proton flow back into the matrix to make ATP from ADP + Pi |
Electron route:
NADH → Complex I → CoQ → Complex III → Cytochrome c → Complex IV → O₂ → H₂O
FADH₂ → Complex II → CoQ → Complex III → Cytochrome c → Complex IV → O₂ → H₂O
Why oxygen is essential
Oxygen is the final electron acceptor. At Complex IV, it accepts electrons and H⁺ to form water:
O₂ + 4e⁻ + 4H⁺ → 2H₂O
Without oxygen, electrons cannot move through the ETC. NADH and FADH₂ cannot be reoxidized, the citric acid cycle slows, ATP production falls sharply, and cells shift toward anaerobic glycolysis with lactate formation.
ATP yield
Approximate yields:
- 1 NADH produces about 2.5 ATP
- 1 FADH₂ produces about 1.5 ATP
NADH yields more because it enters at Complex I, whereas FADH₂ enters at Complex II and bypasses the first proton-pumping step.
Important inhibitors
- Rotenone and amytal: inhibit Complex I
- Malonate: inhibits Complex II
- Antimycin A: inhibits Complex III
- Cyanide, carbon monoxide, azide, hydrogen sulfide: inhibit Complex IV
- Oligomycin: inhibits ATP synthase (Complex V)
Cyanide poisoning is rapidly fatal because it prevents cells from using oxygen even if blood oxygen levels are normal.
Uncouplers
Uncouplers allow H⁺ to return to the matrix without ATP synthesis. Energy is released as heat instead of being captured as ATP.
- Physiological example: thermogenin (UCP1) in brown adipose tissue
- Toxic example: high-dose salicylates
In one sentence: the ETC uses electrons from NADH/FADH₂ to pump protons, and ATP synthase uses the resulting proton gradient to make ATP.