Biochemical lesions of respiratory enzymes and configurational changes of mitochondria in vivo. II. Early ultrastructural modifications correlated to the biochemical lesion induced by fluoroacetate.
Correlative biochemical and electron microscopic alterations were observed in chick embryo myoblasts in vitro after treatment with fluoroacetate. Fluoroacetate poisoning caused an increase of citrate and a decrease of ATP in the cultures. Cell respiration was only slighly impaired by fluoroacetate in the first 10 min but was inhibited to 30% one hour after exposure to the poison. Fluoroacetate did not affect oxidative phosphorylation. The evidence suggests that fluoroacetate was transformed in myoblasts into fluorocitrate which inhibited the mitochondrial-bound aconitate hydratase as in adult tissues. Ultrastructural changes in the majority of the fluoroacetate-treated cells were observed. Very few myoblasts appeared unaffected by the poison. Mitochondria were specifically altered. The early changes occurred in the mitochondrial matrix where the inhibited enzyme is known to be located and were followed by modifications in the configuration and structure of cristae. Exogenous fluorocitrate caused ultrastructural changes in the mitochondria similar to that provoked by fluoroacetate. The localization of the early change in the mitochondrial matrix and the evaluation of the structural modifications suggest a correlation between the biochemical lesion, i.e. the inhibition of aconitate hydratase, and the change revealed in the mitochondrial structure containing the inhibited enzyme.
D000154:Aconitate Hydratase; D000255:Adenosine Triphosphate / Q000032:analysis; D000818:Animals; D002642:Chick Embryo; D002951:Citrates / Q000032:analysis; D005463:Fluoroacetates / Q000494:pharmacology*; D008854:Microscopy, Electron; D008931:Mitochondria, Muscle / Q000187:drug effects* / Q000201:enzymology; D009132:Muscles / Q000473:pathology; D010101:Oxygen Consumption / Q000187:drug effects; D013997:Time Factors
D002951:Citrates; D005463:Fluoroacetates; D000255:Adenosine Triphosphate; D000154:Aconitate Hydratase