Question

What is the difference between uncouplers of oxidative phosphorylation and inhibitors of the Electron transport chain? I need to know how to compare their effects on energy production, O2 consumption, and Electron transport chain function.

Answer 1

Uncoupling of ETC

• Uncoupling of ETC and heat generation in mitochondria is beneficial in cold condition.
• It helps in thermogenesis (non-shivering).
• Uncoupling proteins (UCP) located as integral proteins in inner mitochondrial membrane, results in proton leak, reducing membrane potential and generates heat.
• UCPs are common in hypothalamus, hippocampus, cerebellum, substantia nigra, spinal cord and associated with thermoregulation.
• Uncoupling is related to formation of reactive oxygen compounds associated with mitochondrial respiration.
• These reactive oxygen compounds are measured for their Oxygen uptake in the peripheral blood mono-nuclear cells (PBMNCs).
• The level of oxygen consumption would be reflected coupled mitochondrial respiration (ATP formation per oxygen) and uncoupled oxygen consumption by mitochondria.
• Uncoupling agent used is Carbonyl cyanide p (trifluoromethoxy) Phenyl Hydrazone (FCCP).
• This provides the index of energy reserve capacity.

Mitochondrial inhibitor

• The mechanism of oxidative phosphorylation occurs in mitochondria of live cells. Electrons are transported across various components of electron transport chain (ETC), resulting in series of oxidation-reduction reactions within the membrane bound complexes in mitochondria (complex I, II, II, IV).
• ATP synthase complex, designated as F₀F₁- ATP synthase, is located within the mitochondrial cristae. They help in back flow of proton, creating free energy to generate ATP. ATP synthase is composed of two parts: a) Coupling factor 1 (F₁)- which contains the catalytic subunit of ATP synthase. b) Coupling factor 0 (F₀) – which act as a proton channel between mitochondrial matrix and intramembranous mitochondrial space.
• Inhibitors act on different component of mitochondria, preventing their functions.

Some examples are:

• ATPase and ATP-inhibitors like Rotenone (complex I inhibitor), Antimycin A (complex III inhibitor), Oligomycin (F0 part-inhibitor of ATP synthase).

• This results in decrease in cellular respiration.