Mitochondrial Metabolism and ATP Synthesis

Electron Transport Chain: Complexes III and IV

• Complex III (cytochrome c reductase) functions by reducing the protein cytochrome c through the addition of electrons.

• Complex IV (cytochrome c oxidase) removes electrons from cytochrome c, utilizing their energy to pump hydrogen ions ($H^+$).

• Oxygen ($O_2$) serves as the final electron acceptor, combining with electrons and hydrogen to form water ($H_2O$).

• The two primary waste products of mitochondrial metabolism are carbon dioxide ($CO_2$) and water ($H_2O$).

• Complexes I, III, and IV are physically clustered to minimize the distance carriers must travel.

Electron Carriers: Ubiquinone and Cytochrome c

• Ubiquinone (Coenzyme Q) is an ancient, non-protein carrier found in nearly all eukaryotic cells.

• Cytochrome c contains a heme group with an iron atom that physically carries the electrons.

• Cytochrome c serves as a "molecular clock," as its sequence variations allow scientists to determine the evolutionary distance between organisms.

The Electrochemical Gradient

• Pumping $H^+$ into the intermembrane space creates an electrochemical gradient composed of concentration ($pH$) and electrical voltage differences.

• The intermembrane space becomes more positively charged while the matrix side becomes more negative.

• This gradient provides the driving force for $H^+$ to return to the matrix through specific channels.

Complex V: f1f0 ATP Synthase

• The f1f0 ATP synthase is the enzyme responsible for $ATP$ production.

• Structure components:

  • $f_0$: A transmembrane rotor that acts like a water wheel when $H^+$ passes through it.

  • $f_1$: The ATPase component that joins phosphate to $ADP$.

• Mechanism: The mechanical energy of the spinning $f_0$ rotor powers the chemical reaction to create $ATP$.

• Bidirectionality: If the gradient is imbalanced, the synthase can spin in reverse, breaking down $ATP$ to generate heat rather than chemical energy.

Extended Functions of the Proton Gradient

• The $H^+$ gradient also powers the transport of other essential molecules into the matrix:

  • Pyruvate.

  • Inorganic phosphate.

• A voltage-driven pump uses the membrane's electrical difference to exchange matrix $ATP$ for cytoplasmic $ADP$.

Questions & Discussion

• Question: Why don't hydrogen ions dissipate out through the large pores in the outer mitochondrial membrane?

• Response: There are two reasons. First, the electron transport chain is constantly pumping new hydrogen into the intermembrane space. Second, the electrochemical gradient draws the $H^+$ ions back into the matrix rather than out into the cytoplasm.