Evidence for ADP-ribosylation in the mechanism of rapid thyroid hormone control of mitochondria.
Triiodothyronine in vitro at concentrations between 10(-13) and 10(-11) M very rapidly activates oxidative phosphorylation in hypothyroid rat liver mitochondria. Comparing the concentrations of hormone with estimates of the amounts of respiratory chain components present suggests that this activation may involve an amplification mechanism. Here we present evidence that while no changes in phosphorylation were detected following hormone administration, nicotinamide, an inhibitor of mono ADP-ribosylation reported to occur rapidly and reversibly in mitochondria, prevented activation by hormone. Moreover incubation with nicotinamide of euthyroid mitochondria and derived intact inner membrane vesicles revealed lowered ADP/O ratios under the same conditions as shown by hypothyroid preparations. While this lesion could be reversed simply by washing the intact mitochondria, the membrane vesicles required triiodothyronine addition.
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism*; D000818:Animals; D007037:Hypothyroidism / Q000378:metabolism*; D007425:Intracellular Membranes / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008930:Mitochondria, Liver / Q000502:physiology*; D009536:Niacinamide / Q000494:pharmacology; D010085:Oxidative Phosphorylation; D010750:Phosphoproteins / Q000378:metabolism; D051381:Rats; D013963:Thyroid Hormones / Q000502:physiology*
D008565:Membrane Proteins; D010750:Phosphoproteins; D013963:Thyroid Hormones; D000246:Adenosine Diphosphate Ribose; D009536:Niacinamide