Question

Rotenone is a potent inhibitor of Complex I. Atpenin is a potent inhibitor of Complex II. Which do you expect to inhibit the proton motive force-why? (5 pts)

Answer 1

Electron transport chain (ETC) is a series of complexes that transfer electrons from electron donors to electron acceptors via redox (both reduction and oxidation occurring simultaneously) reactions, and couples this electron transfer with the transfer of protons (H⁺ ions) across a membrane. This creates an electrochemical proton gradient that drives the synthesis of adenosine triphosphate (ATP), a molecule that stores energy chemically in the form of highly strained bonds.

In complex I, NADH dehydrogenase two electrons are removed from NADH and ultimately transferred to a lipid-soluble carrier, ubiquinone (UQ). The reduced product, ubiquinol (UQH₂), freely diffuses within the membrane, and Complex I translocates four protons (H⁺) across the membrane, thus producing a proton gradient. Rotenone inhibits the transfer of electrons from iron-sulfur centers in complex I to ubiquinone. This interferes with the proton transfer across the mitochondrial membrane, thereby inhibiting the proton motive force.

In Complex II, succinate dehydrogenase additional electrons are delivered into the quinone pool (Q) originating from succinate and transferred (via flavin adenine dinucleotide (FAD)) to Q. Complex 2 is a parallel electron transport pathway to complex 1, but unlike complex 1, no protons are transported to the intermembrane space in this pathway. Aptenin is an inhibitor of complex II. Since, complex II is not involved in proton transfer, it does not inhibit proton motive force inspite of being an inhibitor of electron transport chain.