Mitochondria: Structure, Function & Metabolism

Structure

• Mitochondria are usually ovoid intracellular organelles and are particularly numerous in metabolically active cells.
• They contain their own circular double-stranded mitochondrial DNA, predominantly maternally inherited.
• Most mitochondrial proteins are nevertheless encoded by nuclear DNA and imported into the organelle.

Functions

• ATP production by oxidative phosphorylation.
• Citric acid / TCA cycle.
• Fatty-acid β-oxidation.
• Apoptosis regulation.
• Ca²⁺ buffering and cellular calcium homeostasis.
• Thermogenesis through mitochondrial uncoupling, especially in brown adipose tissue.
• Reactive oxygen species generation and signalling.
• Parts of haem synthesis and steroid synthesis.
• Mitochondrial steps of the urea cycle.

Role in carbohydrate metabolism

1. Glycolysis supplies mitochondrial substrate

• Glycolysis occurs in the cytosol: glucose → 2 pyruvate + 2 ATP + 2 NADH.
• Pyruvate is transported into the mitochondrial matrix.

2. Pyruvate oxidation

• In the matrix, the pyruvate dehydrogenase complex converts pyruvate to acetyl-CoA + CO₂ + NADH.
• Acetyl-CoA then enters the citric acid cycle.

3. Citric acid / TCA cycle

• Occurs mainly in the mitochondrial matrix.
• Acetyl-CoA combines with oxaloacetate and is oxidised back to oxaloacetate.
• Each acetyl-CoA generates 3 NADH, 1 FADH₂, 1 GTP and 2 CO₂.
• The key energetic role is generation of NADH and FADH₂, which donate high-energy electrons to the respiratory chain.
• O₂ is not directly consumed by the TCA cycle, but continued cycle activity depends on regeneration of NAD⁺ and FAD by the electron transport chain.

4. Electron transport chain

• Located in the inner mitochondrial membrane.
• NADH donates electrons to Complex I; FADH₂ donates via Complex II.
• Electrons pass via coenzyme Q → Complex III → cytochrome c → Complex IV.
• Complexes I, III and IV pump H⁺ from the matrix into the intermembrane space; Complex II does not pump H⁺.
• At Complex IV, O₂ is the terminal electron acceptor and is reduced to H₂O.

5. Oxidative phosphorylation

• H⁺ pumping creates an electrochemical proton gradient across the inner mitochondrial membrane.
• H⁺ returns to the matrix through ATP synthase.
• ATP synthase couples proton flow to ADP + Pi → ATP.
• Approximate modern yields are ~2.5 ATP per NADH and ~1.5 ATP per FADH₂.
• Complete aerobic oxidation of one glucose yields approximately 30–32 ATP, depending mainly on the shuttle used for cytosolic NADH.