THE CYTOPLASM 243 



mitochondrial fraction of liver may be more heterogeneous biochemically 

 than previous results have indicated. In these experiments, the approach 

 was somewhat different from that of Chantrenne and Xovikoff et al. The 

 mitochondrial fraction was first isolated by the usual procedure, and then 

 particles in the fraction of different specific gravities were segregated by 

 high-speed centrifugation in a sucrose density gradient. It was found that 

 about 75 % of the total nitrogen was recovered in two fractions, in which 

 the concentration of PXA and of several enzymes was almost the same. 

 The finding of greatest interest, however, was that a major part of the uri- 

 case and deoxyribonuclease activities of the original preparation of mito- 

 chondria was associated with particles accounting for only 10 % of the total 

 nitrogen and containing a very low concentration of succinic dehydrogenase. 

 With respect to uricase and succinic dehydrogenase, these results are 

 generally similar to the data reported by Novikoff et al.^^ The latter in- 

 vestigators considered the uricase-containing particles to be microsomal 

 in nature. Independent evidence bearing on the question of the biochemical 

 heterogeneity of mitochondria has come from experiments in which a 

 study was made of the livers of rats fed the noncarcinogenic derivative of 

 butter yellow, 2-methyl-4-dimethylaminoazobenzene.^°^'2"^ It was found 

 that the addition of this compound to the diet resulted in a 2.5-fold increase 

 in the number of mitochondria per unit weight of liver. These mitochondria 

 were normal with respect to succinoxidase content, the activity of this 

 enzyme system having increased to the same extent as did the number of 

 mitochondria, but were deficient in a number of other enzymatic activities 

 studied (octanoic acid oxidase, DPX-cytochrome c reductase, uricase, de- 

 oxyribonuclease, and ribonuclease) . Other investigations have indicated 

 that liver mitochondria can also undergo alterations as a result of hormonal 

 imbalances. The unpublished experiments of Dr. S. H. Wollman of the 

 National Cancer Institute, for example, suggest that the livers of hyper- 

 thyroid rats contain a normal number of mitochondria characterized by a 

 greatly increased ability to oxidize succinic acid, while the livers of diabetic 

 rats contain an increased number of mitochondria having the same suc- 

 cinoxidase activity as do normal liver mitochondria. The results with the 

 diabetic and hyperthyroid livers need to be substantiated, however, by 

 actual counts of the number of liver mitochondria. 



A conclusive demonstration that mitochondria are biochemically hetero- 

 geneous will, if obtained, pose several interesting and important questions. 

 In the first place, would such a finding mean that the mitochondria in each 

 liver cell show varying degrees of differentiation or that the mitochondria 



203 M. J. Striebich, E. Shelton, and W. C. Schneider, Cancer Research 13, 279 (1953). 



204 W. C. Schneider, G. H. Hogebroom, E. Shelton, and M. J. Striebich, Cancer Re- 

 search 13, 285 (1953). 



