Cellular respiration is the process of oxidizing food molecules, like glucose, to carbon dioxide and water. The energy released is coupled to  ATP for use by all the energy-consuming activities of the cell.

2 distinct evolutionary stages are still present:

• glycolysis, the breakdown of glucose to pyruvic acid in the absence of O2
• Kreb's Cycle/oxidative phosphorylation the complete oxidation of pyruvic acid to carbon dioxide and water

In eukaryotes, glycolysis occurs in the cytosol. .
Oxidative phosphorylation takes place in mitochondria.

Mitochondria

Mitochondria are membrane-enclosed organelles distributed through the cytosol of most eukaryotic cells. Their main function is the conversion of the potential energy of food molecules into ATP. Mitochondria have:

• an outer membrane that encloses the entire structure
• an inner membrane that encloses a fluid-filled matrix
• between the two is the intermembrane space
• the inner membrane is elaborately folded with shelf like cristae projecting into the matrix.
• a small number (some 5-10) circular molecules of DNA

The Outer Membrane

The outer membrane contains many complexes of integral membrane proteins that form channels through which a variety of molecules and ions move in and out of the mitochondrion.

The Inner Membrane

The inner membrane contains 5 complexes of integral membrane proteins:

• NADH dehydrogenase
• succinate dehydrogenase
• cytochrome c reductase(also known as the cytochrome b-c₁ complex)
• cytochrome c oxidase
• ATP synthase

The Matrix

The matrix contains a complex mixture of soluble enzymes that catalyze the respiration of pyruvic acid and other small organic molecules.

Here pyruvic acid is

• oxidized by NAD⁺ producing NADH + H⁺
• decarboxylated producing a molecule of
  • carbon dioxide (CO₂) and
  • a 2-carbon fragment of acetate bound to coenzyme A forming acetyl-CoA

The Citric Acid Cycle

• This 2-carbon fragment is donated to a molecule of oxaloacetic acid.
• The resulting molecule of citric acid (which gives its name to the process) undergoes the series of enzymatic steps shown in the diagram.
• The final step regenerates a molecule of oxaloacetic acid and the cycle is ready to turn again.

Summary:

• Each of the 3 carbon atoms present in the pyruvate that entered the mitochondrion leaves as a molecule of carbon dioxide (CO₂).
• At 4 steps, a pair of electrons (2e^-) is removed and transferred to NAD⁺ reducing it to NADH + H⁺.
• At one step, a pair of electrons is removed from succinic acid and reduces FAD to FADH₂.

The electrons of NADH and FADH₂ are transferred to the respiratory chain.

The Respiratory Chain

The respiratory chain consists of 3 complexes of integral membrane proteins

• the NADH dehydrogenase complex
• the cytochrome c reductase complex
• the cytochrome c oxidase complex

and two freely-diffusible molecules

• ubiquinone
• cytochrome c

that shuttle electrons from one complex to the next.

The respiratory chain accomplishes:

• the stepwise transfer of electrons from NADH (and FADH₂) to oxygen molecules to form (with the aid of protons) water molecules (H₂O);

  (Cytochrome c can only transfer one electron at a time, so cytochrome c oxidase must wait until it has accumulated 4 of them before it can react with oxygen.)

• harnessing the energy released by this transfer to the pumping of protons (H⁺) from the matrix to the intermembrane space.
• Approximately 20 protons are pumped into the intermembrane space as the 4 electrons needed to reduce oxygen to water pass through the respiratory chain.
• The gradient of protons formed across the inner membrane by this process of active transport forms a miniature battery.
• The protons can flow back down this gradient, reentering the matrix, only through another complex of integral proteins in the inner membrane, the ATP synthase complex (as we shall now see).

Chemiosmosis in mitochondria

The energy released as electrons pass down the gradient from NADH to oxygen is harnessed by the three enzyme complexes of the respiratory chain to pump protons (H⁺) against their concentration gradient from the matrix of the mitochondrion into the intermembrane space (an example of active transport).

As their concentration increases there (which is the same as saying that the pH decreases), a strong diffusion gradient is set up. The only exit for these protons is through the ATP synthase complex. As in chloroplasts, the energy released as these electrons flow down their gradient is harnessed to the synthesis of ATP. The process is called chemiosmosis and is an example of facilitated diffusion.

One-half of the 1997 Nobel Prize in Chemistry was awarded to Paul D. Boyer and John E. Walker for their discovery of how ATP synthase works.