Cell Damaee 75 



"5 



the mitochondrial membrane, as originally suggested by Christie 

 and Judah, but the mechanism for this still eludes us. Several work- 

 ers have remarked upon the similarity of action of CC1 4 with that 

 of inorganic phosphate which also makes mitochondria swell up, 

 lose DPN in vitro and acquire Avater (Recknagel and Malamed, 

 1958) . Ca ions would appear to be of importance in these responses. 

 A ten-fold increase in concentration of Ca ions occurs in the mito- 

 chondria sixteen to twenty hours after exposure to CC1 4 (Thiers 

 and Reynolds, 1958) . Calcium ions release DPN from mitochon- 

 dria in vitro (Ernster, 1956) . It is possible, therefore, that the in- 

 creased concentration of Ca ions in the liver in CC1 4 poisoning is 

 the cause of the mitochondrial change. This may be due to these 

 ions interfering with the binding of reduced pyridine nucleotides 

 to mitochondria (Chance and Conrad, 1958) . However, the loss of 

 DPN from mitochondria exposed to CC1 4 in vitro cannot be re- 

 ferred wholly to calcium, for it happens when mitochondria are 

 suspended in a calcium-free medium. Moreover, mitochondrial 

 damage can be diminished by the administration of ethylene 

 diaminotetroacetate (versene) which inhibits the Ca ion accumula- 

 tion but does not prevent the fatty change (Calvert and Brody, 

 1958) . It is difficult to escape from the feeling that many of these 

 in vitro abnormalities of mitochondria isolated from rats poisoned 

 by CC1 4 are artefacts due to calcium ions concentrating in the 

 organelles. Such experiments may not represent accurately the be- 

 haviour of mitochondria in the living cell. Nevertheless, mitochon- 

 drial injury does occur since liver enzymes that are localised 

 specifically in the mitochondria leak into the blood during CC1 4 

 poisoning though this happens at a relatively late period (Rees and 

 Sinha, 1961) . Perhaps CC1 4 — a fat solvent— disturbs the lipoprotein 

 of the mitochondrial membranes that occupy an essential place in 

 the enzymic mechanism of these organelles (Green, 1959) . 



The story has taken a new turn as the result of recent investiga- 

 tions in our laboratory by Judah and Rees (1959) . Reference to 

 the chapter on Fats will remind the reader of the essential stages 

 of lipid synthesis in the cell and recall the importance of choline 

 in diverting diglyceride, through the action of transferase, in the 

 proper direction of lecithin (Fig. 1) . When this diversion is pre- 



