Regulation of Oxidative Phosphorylation

Introduction Thyroid hormones (TI Is) affect cellular metabolism via two different pathways. The first one is the socalled nuclear, long-term effect: there the TI I binds to a nuclear receptor and regulates the transcription o f multiple cellular proteins f 11. The other pathway, the short-term extranuclear pathway, is less w d l defined and could in principle be similar to other short-term signalling pathways, that is, the signal originates in the binding of TI1 to a plasmamembrane receptor, which generates an intracellular messenger that induces changes in metabolism, via phos~~horylatic,n-dephosphorylation of enzymes and of proteins 121. I Iowever, with 7’Hs it is also feasible that they interact directly with intracellular proteins since they can enter the cell [ 3 ] . Interestingly. several parameters. especially those relating to bioenergetics, are affected in a similar way in the short-term range as well as in the long-term range. I hus, respiration is stimulated in the long-term range in euthyroid or hyperthyroid states, as well as within minutes in the presence of 1.-triiodothyronine (Ti) [ 41. This stirnulatory effect of 7’1 1s is oligomycin-sensitive, indicating that it is not due t o an uncoupling action of 7’Hs [ 41. Likewise glucose production is increased in liver in the short-term range 1.51, as well as in euthyroid or hyperthyroid states [ 4 1. W e also found that the distribution of adenine nucleotides is changed in a similar way by TI Is. both in hyperthyroid livers and in perfused liver after the direct infusion of T3 161. The niitochondrial A?’P/AI>P ratio is decreased both in vi710 and in vitro, whereas the cytor .