Rotenone blocks electron transfer from Complex I to ubiquinone. If isolated mitochondria are supplied with pyruvate and malate as substrates, what is the immediate consequence of rotenone addition?
- A All TCA cycle activity stops immediately
- B FADH2 oxidation through Complex II continues normally and ATP synthesis is unaffected
- C NADH accumulates, the NADH/NAD+ ratio rises, and TCA cycle dehydrogenases become inhibited ✓
- D Electrons from succinate cannot enter the ETC
Correct answer: C. NADH accumulates, the NADH/NAD+ ratio rises, and TCA cycle dehydrogenases become inhibited
Explanation
Pyruvate and malate generate NADH via TCA cycle dehydrogenases. Rotenone blocks NADH re-oxidation at Complex I, causing NADH accumulation and a high NADH/NAD+ ratio. This inhibits NAD+-dependent dehydrogenases (isocitrate DH, alpha-ketoglutarate DH, pyruvate DH), slowing the TCA cycle. Distractor A is wrong because the cycle slows, not stops immediately. Distractor B is wrong because while succinate oxidation continues, overall ATP synthesis is reduced.
Reference: Lehninger Principles of Biochemistry, 7th ed.
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