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EFFECTS OF OSMOLAR CHANGES ON ISOLATED MITOCHONDRIA OF BRAIN AND LIVER
Authors:D Holtzman    N Lewiston    M M Herman    M Desautel    E Brewer  E Robin
Institution:Departments of Neurology, Pediatrics, Pathology (Neuropathology), and Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Abstract:Abstract— The effects of altered osmolarity on respiration and fine structure were compared in isolated rat cerebral versus liver mitochondria.
Polarographic study of cerebral mitochondria in hypo-osmolar media showed inhibition of State 3 (ADP-dependent) respiration which was not reversed by dinitrophenol. In hyperosmolar media, State 3 respiration was transiently inhibited and State 4 (ADP-independent) respiration increased with the NAD-linked substrate pair, glutamate and malate. With succinate as substrate, respiration was not affected by moderate hyperosmolarity. In the most hyperosmolar medium, State 3 respiration was inhibited with both substrates.
In contrast to the results with cerebral mitochondria, State 4 respiration was increased in hypo-osmolar media and State 3 respiration was persistently inhibited in hyperosmolar media in liver mitochondria with both substrates.
In both cerebral and liver mitochondria, cytochrome c oxidase (EC 1.9.3.1.) activity was mildly inhibited in hypo-osmolar media and increased in hyperosmolar media.
Electron microscopy showed that liver mitochondria were swollen in hypo-osmolar media and condensed in hyperosmolar media. Cerebral mitochondria showed mild rarefaction in hypo-osmolar media and, in hyperosmolar media, more than half the mitochondria showed either no or minimal changes in fine structure.
Our results suggest that there are differences in metabolic control and structure between mitochondria from different cell types, which may be important in the cellular metabolic response to pathologic changes in water or osmolarity.
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