During the past years many efforts have been made to elucidate the origin of the uncoupling mechanisms induced by hyperthyroidism in mitochondria. Two main mechanisms have been proposed: a classical protonophoric uncoupler mechanism, considering the action of thyroid hormones at the level of the lipid membrane bilayer, and a slipping mechanism with more localized effects at the level of the redox proton pumps. This short review is devoted to comparing and discussing the evidence against and in favour of these two mechanisms.

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