Mitochondrial Function and Oxidative Phosphorylation

Key Processes in Oxidative Phosphorylation

• Oxidation
  • Involves electron flow
• Phosphorylation
  • Synthesis of ATP from ADP and inorganic phosphate (Pi)
• Coupled Processes:
  • Both oxidation and phosphorylation occur together, facilitated by electron transport chain (ETC).

Mechanism of Electron Transport Chain

• Electrons:

  • Transferred from NADH to O2 through the electron carriers in the mitochondrial inner membrane.
  • The process involves electron flow and proton movement (from the mitochondrial matrix to the intermembrane space).
  • The energy released during electron transfers is used to pump protons across the membrane, creating a proton gradient.

• Electron Carriers:

  • Primarily metals like iron (Fe) and copper (Cu), existing in a chelate form (as heme or Fe-S complex).
  • Carriers can change oxidation states to mediate electron transfers (Fe: 2+ to 3+).

ATP Synthase Mechanism

• F1F0 ATP Synthase:
  • Comprises two main components: F0 (membrane-embedded part) and F1 (ATP synthesis site).
  • Protons flow through F0, driving conformational changes that synthesize ATP at F1.
  • ATP synthesis involves binding change mechanism.

Proton Gradient Generation

• Complexes of the ETC:
  • Complex I (NADH-Q reductase):
  • Transfers electrons from NADH to ubiquinone (Q) and pumps protons across the inner mitochondrial membrane.
  • Complex II (Succinate Dehydrogenase):
  • Transfers electrons from succinate to Q, does not pump protons.
  • Complex III (Q-cytochrome c reductase):
  • Takes electrons from QH2 and reduces cytochrome c, contributing to the proton gradient.
  • Complex IV (Cytochrome c oxidase):
  • Reduces O2 and pumps protons into the intermembrane space.

Inhibitors of Electron Transport Chain

• Rotenone, Malonate, Antimycin A, Cyanide:
  • Serve as inhibitors in various complexes of the electron transport chain.

Generation of Reactive Oxygen Species (ROS)

• Superoxide Formation:
  • Can occur from the reaction of oxygen with electrons in the ETC, leading to potential cellular damage.
  • Cellular systems inactivate superoxide via enzymes like superoxide dismutase and catalase.

Transport Mechanisms in Mitochondria

• Adenine Nucleotide Translocase:
  • Exchanges ATP from the matrix for ADP from the cytosol.
• Phosphate Exchange:
  • Two main pathways for Pi transport in the inner membrane:
  1. Pi-/H+ cotransporter
  2. Malate/Pi exchange.

Shuttling Mechanisms for NADH

• Glycerol Phosphate Shuttle:
  • Transfers electrons from cytosolic NADH into the mitochondria indirectly.
• Malate/Aspartate Shuttle:
  • Involved in transporting oxaloacetate-derived electrons into the mitochondria.

Summary of Key Points

• Oxidative phosphorylation is driven by the electron transport chain and creates ATP through a coupled proton gradient mechanism.
• Understanding the role of various complexes and the mechanisms of ATP synthesis is crucial for grasping mitochondrial function and energy production.