The prevention of swelling of liver mitochondria in vitro

Abstract

The swelling of rat-liver mitochondria which occurs during incubation at 28[degree] can be largely prevented by adenosine triphosphate (ATP) and adenosine monophosphate (AMP) in the presence and absence of substrate. Aerobic metabolism or oxidative phos-phorylation is not required to maintain a low water content of mitochondria. Mg2+ and Mn2+ ions largely protect mitochondria from swelling. Both Mg2+ and Mn2+ ions enhance and prolong the action of AMP, and both these ions and AMP are antagonized by Ca2+ ions and by inorganic orthophosphate. Added Na+, K+, Cl" and SO42" ions in the range 1-10 m[image] are without effect, and citrate, oxalate and ethylenediaminetetraacetate protect mitochondria from swelling. The effects of the nucleotides, Mg2+ and Mn2+ ions on the water content of mitochondria are also appreciable in a medium consisting of only 40 m[image] sucrose. In this medium AMP is more effective than adenosine diphosphate (ADP), which is better than ATP, apparently because of the inhibitory effect of the inorganic phosphate liberated during incubation. All three nucleotides are broken down to adenosine and inorganic phosphate, and this breakdown is more rapid in the presence of Mg2+, Mn2+ and Ca2+ ions either alone or in mixtures. Adenosine 3[image]-phosphate, inosine 5[image]-phosphate, guanosine 5[image]-phosphate, uridine 5[image]-phosphate, flavin monucleotide, adenosine and inosine were without effect on the water content of mitochondria. It is concluded that the agents which prevent swelling act on the structure of the mitochondria in ways which are not yet understood.