Oligomycin is an antibiotic that tightly binds the Fo subunit of ATP synthase (complex V), blocking the proton channel through which H+ flows back into the matrix. What is the expected effect on electron transport chain activity and membrane potential in isolated mitochondria treated with oligomycin?

• A ETC activity increases as proton gradient dissipates; membrane potential decreases
• B ETC activity is unchanged; only ATP synthesis is blocked
• C ETC activity stops and membrane potential decreases simultaneously
• D ETC activity stops as the proton gradient builds to its maximum (hyperpolarisation); membrane potential increases ✓

Explanation

Oxidative phosphorylation is tightly coupled: ETC proton pumping and ATP synthase-mediated H+ re-entry are interdependent. When oligomycin blocks the Fo proton channel of ATP synthase, H+ cannot re-enter the matrix through complex V. This causes the proton gradient (ΔΨm) to increase (hyperpolarisation) because protons continue to be pumped out by complexes I, III, and IV initially but cannot be dissipated. As ΔΨm rises, the electrochemical gradient opposes further proton pumping — the 'back pressure' stalls ETC complexes. Therefore both ETC activity and O2 consumption fall, and state 3 respiration ceases. Addition of an uncoupler (like DNP) after oligomycin would restore ETC activity.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

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