Studies on the rapid stimulation of mitochondrial respiration by thyroid hormones.
Injection of L-3,5-diiodothyronine (T2) into rats made hypothyroid by 6-n-propyl-2-thiouracil (PTU) increased the respiration rates of subsequently isolated liver mitochondria; this stimulation of respiration by T2 occurred in the presence of cycloheximide and is therefore independent of protein synthesis on cytoplasmic ribosomes. Injection of T3 into PTU-treated rats had a lesser effect than T2 on the respiration rates of subsequently isolated mitochondria; as PTU is an inhibitor of 5'-iodothyronine deiodinases, which convert T3 into T2 in vivo, the rapid stimulation of mitochondrial respiration by T3, which has been shown in a range of systems, may not be due directly to T3 itself, but may be mediated by its deiodination product T2. Injection of T2, or T3, into hypothyroid or euthyroid rats had no effect on the percentage activity of mitochondrial pyruvate hydrogenase assayed 30 min later. The amount of active pyruvate dehydrogenase is regulated by changes in mitochondrial calcium concentration and matrix ATP/ADP ratio; therefore these parameters are not persistently affected by treatment with T3 or T2. In addition, the total amount of pyruvate dehydrogenase present was the same in euthyroid and hypothyroid rats, indicating that the expression of this enzyme is not stringently controlled by thyroid hormone status.
O'Reilly
I
I
Department of Biochemistry, Trinity College, Dublin, Ireland.
Murphy
M P
MP
D000244:Adenosine Diphosphate / Q000032:analysis; D000255:Adenosine Triphosphate / Q000032:analysis; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology; D004104:Diiodothyronines / Q000494:pharmacology*; D007037:Hypothyroidism / Q000139:chemically induced / Q000201:enzymology / Q000503:physiopathology; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D011441:Propylthiouracil; D011768:Pyruvate Dehydrogenase Complex / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014284:Triiodothyronine / Q000494:pharmacology*
D004104:Diiodothyronines; D011768:Pyruvate Dehydrogenase Complex; D014284:Triiodothyronine; D000244:Adenosine Diphosphate; D011441:Propylthiouracil; D000255:Adenosine Triphosphate; D003513:Cycloheximide; D002118:Calcium