DNP (2,4-dinitrophenol) is an effective weight-loss agent that was used in diet pills in the 1930s. It has since been removed from the market (though it is available online) because of serious side effects such as fever, cataracts, rashes and sometimes death. DNP inserts into the inner mitochondrial membrane and shuttles protons between the intermembrane space into the matrix. What will happen to ATP production, the proton gradient, and the pH of the various mitochondrial compartments?

During oxidation of FADH2 and NADH, electrons are transferred through electron transport chain to the terminal electron acceptor, molecular oxygen. Electron transfer by the electrons carriers of electron transport chain is accompanied by the pumping of protons from matrix to the intermembrane space and generation of the proton concentration gradient. The proton concentration gradient drives ATP synthesis.

According to the given information, DNP shuttles protons from the intermembrane space into the matrix and thereby, lowers down the pH of the matrix making it more acidic with respect to intermembrane space. This would dissipate the proton concentration gradient and there will be reduced or no ATP production in the absence of the driving force.