Autolysis 99 



half its value during the second day. Ischaemic release of hydrolases 

 may be the outcome of an anoxic change in the intracellular en- 

 vironment of the lysosomes which is quite likely reflected in a lower- 

 ing of pH. Possibly there is a primary attack on the lysosomal mem- 

 brane with extension of autolysis from these centres, as the released 

 enzymes diffuse away. Lowering of pH, which is known to acceler- 

 ate the breakdown of lysosomes in vitro, may involve the particles' 

 own cathepsin acting on the membrane from the inside. Mitochon- 

 drial cytochrome oxidase and microsomal glucose-6-phosphate also 

 are inactivated during autolysis. De Duve records release of lyso- 

 somal hydrolases in the liver of rats after starvation, poisoning by 

 carbon tetrachloride, dietary deficiency, ligation of the common 

 bile duct, especially when the animals are comatose. All such re- 

 sults, he believes, confirm the hypothesis that the opening of lyso- 

 somes, and the consequent release of their internal enzymes, plays 

 an important part in the intiation of autolysis. Enzymic alterations 

 may precede by several hours the manifestation of well-defined 

 microscopical lesions. 



Our information about autolysis in other organs is extremely 

 limited, but where available it agrees fairly well with that obtained 

 from liver investigations. Thus, the autolysing or ischaemic kidney 

 loses succinic dehydrogenase, phosphatases, esterases and lipases, 

 the brain, phosphatases. But the subject badly needs re-investiga- 

 tion with modern techniques. 



In our own laboratory factors influencing the survival of liver 

 cells during autolysis have been studied by the artificial perfusion 

 technique applied to the rat (Gallagher et ah, 1956; Dawkins, 

 Judah and Rees, 1959) . Previous investigations had convinced our 

 colleagues that early autolysis is accompanied by a great increase in 

 wet weight and accumulation of calcium ions in the cells. At this 

 time cloudy swelling and vacuolation of the cytoplasm are the usual 

 microscopical findings. Dawkins et al., attributed these changes to 

 a failure of the liver cells to maintain osmotic balance because of 

 an inadequate quota of ATP. Homogenates prepared from such 

 autolysing livers certainly fail to couple oxidation with phos- 

 phorylation. This topic is dealt with elsewhere (See "Enzymes," 

 Chapter 5) . 



