Effects of Thyroxine and Related Compounds on Liver 

 Mitochondria in Vitro*t 



Olov Lindberg, Hans Low, Thomas E. Conover,| and Lars Ernster 



The Wenner-Greu Institute for Experimental Biology, 

 University of Sfockliohn, Sweden 



I. Historical Survey 



A first although not successful attempt to demonstrate an effect of 

 thyroxine on oxidative phosphorylation in mitochondria was reported by 

 Judah and Williams- Ashman [i] in 195 1. Later the same year Judah [2] 

 demonstrated a slight effect on the P/0 ratio of liver mitochondria isolated 

 from thyroxine-treated rats. He also compared the effect of thyroxine 

 with that of 2,4-dinitrophenol, and pointed out that no similarity existed 

 between the modes of action of the two compounds. At about the same 

 time Martins and Hess [3] briefly reported that thyroxine, either adminis- 

 tered in vivo or added in vitro, lowered the phosphorylation of isolated rat 

 liver mitochondria. Niemeyer et al. [4], however, found no effect on the 

 P/0 ratio of liver mitochondria from rats treated with thyroxine in vivo, 

 but were able to demonstrate a significant decrease of the respiratory 

 control by phosphate acceptor in these mitochondria. 



In the first comprehensive work on thyroxine eflect in vitro. Lardy and 

 Feldott [5] demonstrated in 195 1 that this compound at a concentration 

 of io~'^ M inhibited the oxidation of glutamate and of certain other DPN- 

 linked substrates by a washed residue of homogenized rat kidney. The 

 inhibition could be partly relieved by added DPN. LTsing particulate 

 preparations of rat liver, a certain extent of decrease of the P/0 ratio was 

 also noticed, both when thyroxine was added in vitro, and in preparations 

 from hyperthyroid animals. The following year Lardy [6] advanced the 

 hypothesis that the hormonal effect of thyroxine resides in its capacity to 

 uncouple one, rate-limiting, phosphorylation from the respiration, thus 

 enhancing both respiratory rate and net output of high-energy phosphate 



* This work has been supported by grants from the Swedish Medical Research 

 Council and the Swedish Cancer Society. 



t Abbreviations: ADP, adenosine diphosphate; ATP, adenosine triphosphate; 

 DPN, diphosphopyridine nucleotide; DPNH, reduced diphosphopyridine 

 nucleotide; TPXH, reduced triphosphopyridine nucleotide. 



\ Fellow of the National Foundation. Present address : Public Health Research 

 Institute of the City of Netv York, Netv York, N.Y., U.S.A. 



