Through the use of combined spectrophotometric and electron microscope techniques, large amplitude swelling of rat liver mitochondria has been described as an ordered sequence of ultrastructural transitions. Prior to the actual swelling, mitochondria undergo two major conformational changes: condensed to twisted form and twisted to orthodox form. This sequence is independent of (a) the nature of swelling agents and (b) the time of onset of swelling. Agents that delay the onset of swelling act to increase the duration of the twisted conformation. Agents that prevent extensive swelling hold mitochondria in intermediate conformations. Gross swelling, immediately preceded by a decrease in electron opacity of the matrix, involves the rupture of the outer membrane and expansion of the inner compartment of the mitochondrion.

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