Oligomycin, an antibiotic, inhibits the F0 subunit of ATP synthase. Administration of oligomycin to isolated mitochondria would be expected to cause which combination of effects?
- A Decreased oxygen consumption, decreased ATP production, increased proton gradient ✓
- B Increased oxygen consumption, decreased ATP production
- C Increased proton gradient across inner mitochondrial membrane with increased ATP synthesis
- D Uncoupled electron transfer with heat generation and decreased ATP
Explanation
Oligomycin blocks the proton channel (F0 subunit) of ATP synthase, preventing protons from flowing back into the matrix. This maintains (increases) the proton-motive force (electrochemical gradient) across the inner mitochondrial membrane. Since the electron transport chain uses the gradient to drive electron transfer (the gradient back-pressures ETC), a maximal gradient slows electron transfer and O2 consumption. ATP synthesis also stops because protons cannot flow through F0. This is the hallmark of a 'coupled' inhibitor — both O2 consumption and ATP synthesis decrease, and the proton gradient rises. This contrasts with uncouplers (e.g., DNP) which increase O2 consumption while abolishing ATP synthesis.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
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