title: Studies on the pathogenesis of cell injury: effects of inhibitors of metabolism and membrane function on the mitochondria of Ehrlich ascites tumor cells.
abstract: The effects of cell injury on Ehrlich ascites tumor cell mitochondria were studied using two model injuries: (1) interference with cell membrane function and (2) inhibition of ATP synthesis with specific mitochondrial inhibitors. These studies indicate a good correlation between level of ATP and number of swollen mitochondria and between swollen mitochondria and occurrence of flocculent densities. No correlation existed between total ADP level and percentage of condensed mitochondria if all ADP values were considered, although a biphasic relationship appeared to exist between the number of condensed mitochondria and the levels of ATP. The study suggests a reproducible sequence of mitochondrial events following either inhibition of ATP synthesis or induction of cell membrane permeability with the nonpenetrating, membrane-damaging agent p-chloromercuribenzene sulfonic acid. These include the rapid appearance of condensed mitochondria, the reinflation of these to resemble orthodox mitochondria, and the occurrence of high amplitude swelling followed by flocculent densities or calcification, or both. Calcification did not occur when ATP synthesis was inhibited but did occur when the cell membrane was damaged with p-chloromercuribenzene sulfonic acid. It is suggested that the early mitochondrial condensation is related to loss of ions and water from the mitochondrial inner compartment following inhibition of active accumulation systems. It is furthermore suggested that the appearance of the condensed mitochondrial state can be taken as evidence of the intactness of the mitochondrial respiratory chain. The occurrence of swelling indicates structural changes in the mitochondrial inner membrane which occur following loss of ability for ATP synthesis.
mesh_terms: D000244:Adenosine Diphosphate / Q000032:analysis; D000249:Adenosine Monophosphate / Q000032:analysis; D000255:Adenosine Triphosphate / Q000032:analysis / Q000096:biosynthesis; D000818:Animals; D000968:Antimycin A / Q000494:pharmacology*; D002286:Carcinoma, Ehrlich Tumor / Q000473:pathology*; D002462:Cell Membrane / Q000187:drug effects* / Q000502:physiology; D002463:Cell Membrane Permeability / Q000187:drug effects; D004140:Dinitrophenols / Q000494:pharmacology*; D007461:Iodoacetates / Q000494:pharmacology*; D008628:Mercury / Q000494:pharmacology; D051379:Mice; D008854:Microscopy, Electron; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008933:Mitochondrial Swelling / Q000187:drug effects; D009942:Organometallic Compounds / Q000494:pharmacology; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D013439:Sulfhydryl Reagents / Q000494:pharmacology
chemical_list: D004140:Dinitrophenols; D007461:Iodoacetates; D009942:Organometallic Compounds; D013439:Sulfhydryl Reagents; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D000968:Antimycin A; D000255:Adenosine Triphosphate; D008628:Mercury