ETC Inhibitors, Uncouplers, and Transporter Inhibitors of Oxidative Phosphorylation

Site of Action Inhibitors / Uncouplers Mechanism Mnemonic for Easy Recall
Complex I (NADH Dehydrogenase) Rotenone, Piericidin A, Amytal Blocks electron transfer from NADH to CoQ “Rotten Pies Available”
(Rotenone, Piericidin A, Amytal block Complex I)
Complex II (Succinate Dehydrogenase) Malonate, Carboxin, TTFA Competes with succinate, preventing electron transfer to CoQ “Malonate Causes Trouble Fast”
(Malonate, Carboxin, TTFA block Complex II)
Complex III (Cytochrome bc1) Antimycin A, BAL Inhibits electron transfer from CoQ to cytochrome c “Anti-BAL for Three”
(Antimycin, BAL block Complex III)
Complex IV (Cytochrome c Oxidase) Cyanide (CN⁻), Carbon Monoxide (CO), Azide (N₃⁻), Hydrogen Sulfide (H₂S) Prevents oxygen from acting as the final electron acceptor “Certain Compounds Attack Hearts”
(Cyanide, CO, Azide, H₂S)
ATP Synthase (Complex V) Oligomycin Blocks proton flow through ATP synthase “O for ATP”
(Oligomycin blocks ATP production)
Uncouplers (Chemical) DNP, Aspirin, Calcium ions Dissipate the proton gradient, generating heat without ATP production “Do Not Push Aspirin or Calcium

(DNP, Aspirin, Calcium ions)

Uncouplers (Physiological) Thermogenin (UCP1), Fatty Acids, Thyroxine Disrupt the proton gradient to generate heat (brown adipose tissue) “The Fat Tissue Uncouples”
(Thermogenin, Fatty acids, Thyroxine)
ADP/ATP Transporter Inhibitors Atractyloside, Bongkrekic Acid Inhibit the ADP/ATP exchange across the inner mitochondrial membrane “A Tricky Bong Blocks ATP”
(Atractyloside, Bongkrekic Acid inhibit ADP/ATP exchange)
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