Control Points in Phosphorylating Respiration 139 



questions (Lehninger, 1955). One explanation is that mito- 

 chondria contain two sets of respiratory carriers, one set of 

 which is obhgatorily coupled to uptake of ADP and Pj, and 

 the other purely non-phosphorylating; in fresh mitochondria 

 the former set dominates, in disrupted mitochondria the 

 second set replaces the first. This appears to be an unlikely 

 mechanism. A second alternative is that the three specific 

 carriers which normally participate in energy coupling and 

 thus in respiratory control by ADP are "shunted out" of the 

 respiratory chain following mitochondrial damage, with 

 formation of non-phosphorylating "short-circuits" around the 

 normally phosphorylating carriers (as may be true in the case 

 of cytochrome b). These shunts could be made possible by the 

 relative non-specificity of electron donors and acceptors in the 

 chain. A third possibility is that the same set of carriers 

 participates in both non-phosphorylating and in phosphory- 

 lating respiration, but that activation of an uncoupling 

 enzyme in disrupted mitochondria releases the chain from 

 dependence on ADP and Pj. There is some evidence sup- 

 porting both the second and third alternatives and it is 

 possible that both mechanisms are involved in the general 

 phenomenon. 



Mitochondrial factors which uncouple phosphorylation and 

 stimulate ATPase have been described by Pullman and 

 Racker (1956) and by Polls and Shmukler (1957), whose 

 factors may well be identical. The latter authors have pre- 

 sented evidence that their factor, called mitochrome, is a 

 haemprotein. More recently Hulsmann, Elliott and Rudney 

 (1958) have shown that the uncoupling activity of such mito- 

 chrome preparations resides in an ^50octane-ext^actable 

 fraction of the protein. Such isooctane extracts of mitochrome 

 have been reported to uncouple phosphorylation in intact 

 rat liver mitochondria, to stimulate ATPase activity and to 

 inhibit the ATP-^^Pj exchange reaction, properties which are 

 in general similar to those of DNP. The activity of these 

 factors is characteristically abolished by serum albumin, 

 which is also capable of restoring phosphorylation in aged 



