Electron Transport System and Formation of ATP

The electron transport chain (ETC) is the main source of ATP production in the body and is vital for life. The earlier stages of respiration generate electron-carrying molecules, such as NADH, to be used in the ETC. Clinically, some molecules interfere with the electron transport chain, which can be life-threatening. Electron Transport System and Formation of ATP is discussed below.


The electron transport chain is located in the mitochondria. There are five main protein complexes in the ETC, located on the inner membrane of the mitochondria. These are called Complexes I, II, III, IV, and V. The two-electron carriers, NADH and FADH2, begin the chain by donating their electrons to Complex I and Complex II, respectively. These electrons then go on to the next complex in the chain.

This process generates energy that is used to pump hydrogen ions into the intermembrane space. In doing so, a proton motive force is generated. This is an electrical and chemical gradient of hydrogen ions between the intermembrane space and the matrix. The main pathway for protons to re-enter the matrix is ​​through ATP synthase, or Complex V. This is key to both pathological and physiological processes and is discussed in Uncoupling.

ATP synthase allows the cell to unload and use the proton motive force. This energy generated by hydrogen ions diffusing back into the matrix through Complex V is harnessed, thus creating ATP from ADP. When the concentration of ATP increases, there is less ADP for ATP synthase to use. Therefore, there is a natural limitation on periods of high respiration to prevent large amounts of ATP from being produced. Conversely, when the ADP concentration is high, there is plenty of ADP for ATP synthase to use, and therefore more ATP is produced.

The electrons, meanwhile, combine with hydrogen and oxygen ions to form water by Complex IV. However, this process is not perfect. Electrons can escape from the electron transport chain and can reduce oxygen, which can produce free radicals such as superoxide and hydrogen peroxide.


Uncoupling proteins provide an alternative route for proteins to pass through the membrane into the matrix. This is due to the reduction of the gradient between the matrix and the intermembrane space. Therefore, less ATP is formed and, instead, more heat is generated.

Physiologically, thermogenin is an uncoupling protein found in brown adipose tissue that allows protons to flow from the intermembrane space into the matrix to generate heat in response to cold. This is especially important in young babies.

Step 1: Generation of a Proton Motive Force

  • Hydrogen carriers (NADH and FADH2) are oxidized and release high-energy electrons and protons.
  • Electrons are transferred to the electron transport chain, which consists of several transmembrane carrier proteins.
  • As the electrons pass through the chain, they lose energy, which the chain uses to pump protons (H+ ions) from the matrix.
  • The accumulation of H+ ions within the intermembrane space creates an electrochemical gradient (or proton motive force)

Step Two: ATP Synthesis Through Chemiosmosis

  • The proton motive force will cause the H+ ions to move down their electrochemical gradient and diffuse back into the matrix.
  • This diffusion of protons is called chemiosmosis and is facilitated by the transmembrane enzyme ATP synthase.
  • As H+ ions move through ATP synthase, they trigger molecular rotation of the enzyme, synthesizing ATP.

Step Three: Oxygen Reduction

  • For the electron transport chain to continue to function, deenergized electrons must be removed
  • Oxygen acts as the final electron acceptor, removing de-energized electrons to prevent the chain from blocking.
  • Oxygen also binds to free protons in the matrix to form water; removal of the protons from the matrix maintains the hydrogen gradient.
  • In the absence of oxygen, hydrogen carriers cannot transfer energized electrons to the chain, and ATP production stops.