Thyroid Hormone Action on Mitochondria. I. Effects of Inhibitors of Respiration", !!:£.h

Measurements of f luorescence at>420 nm and extracted NADPH in mitochondr ia obtained f rom the livers of hypothyro id rats show that the addit ion of Pi, ADP and glutamate rapidly reduces over 90 % of the total reducible intrinsic pyridine nucleotides in State 3, compared with 20 % in normals. The total f luorescence intensity change and reducible NADP + is about twice normal in hypothyro id mitochondria. Adding 6-30 #M L-thyroxine to hypothyro id mitochondr ia in vitro decreases and delays the substrate- induced reduct ion of pyridine nucleotides, and excludes both NADP + f rom such reduct ion and NADPH from oxidat ion by added ADP + Pi, w i thout changing the high NADP(H) content. The correcting actions of the hormone are rapidly reversed by albumin, probably by binding free hormone. Changes in respiration do not appear to account for these observations. There is indirect evidence for decreased phosphory lat ion of added ADP in hypothyro id mitochondr ia, and a correction by added hormone. The hormonal actions on NADP(H) redox reactions are not reproduced by 1 to 6 / IM dinitrophenol in vitro. L-Thyroxine appears to specifically block the participation of NADP(H) in redox reactions in mitochondr ia f rom hypothyro id rats, perhaps by effecting a sequestrat ion of the nucleotide, by inhibit ing the pyridine nucleotide transhydrogenase, or by activating an energy-l inked process that competes with t ranshydrogenat ion