The shocking consequences of defective ionic translocation in mitochondria

Abstract

Evidence is presented to advance the thesis that the condition of shock appears to arise from an attenuation of translocation, the enzymically-catalysed movement of essential metabolites in and out of mitochondria. The concept is supported by (1) the effects in the whole animal of the poisons bongkrekic acid and atractyloside, which inhibit the movement of adenine nucleotides across the inner mitochondrial membrane, (2) alterations in mitochondrial morphology and metabolism in shock, (3) changes in the concentrations of blood constituents, indicating derangement of translocation, and (4) chemical repair of attenuated metabolic traffic across the inner membrane. The multiple origins of the shock syndrome are discussed in terms of a final common pathway, the chief events in which appear to be as follows: injury leads to elevated, sustained secretion of catecholamines, which in turn release non-esterified fatty acids which are then taken up by target organs. Inhibition of the adenine nucleotide translocase by coenzyme A derivatives of long-chain fatty acids seems likely to constitute an important mechanism in the development of shock.