Two types of swelling-shrinkage change manifested by isolated mammalian heart mitochondria have been studied. One type, designated as phase I or "low amplitude" swelling-shrinkage, is estimated to lead to changes in mitochondrial volume of 20 to 40 per cent, to changes in light scattering of about 30 per cent, and to changes in viscosity. These physical changes in mitochondria are brought about rapidly and reversibly by normal reactants of the respiratory chain. Their speed, specificity, and reversibility indicate that they are closely geared to the normal function of the respiratory chain and are a true reflection of a mechanochemical coupling process characteristic of the physiology of mitochondria. A second type of swelling-shrinkage mechanism, designated as phase II or "high amplitude," leads to changes in light scattering, viscosity, and mitochondrial volume which, frequently but not always, are of higher magnitude than the phase I type. Phase II swelling-shrinkage seems to be only partly under the control of the respiratory chain. Prior to the completion of phase II swelling, a stepwise loss of mitochondrial function can be identified, such as changes in the rate of substrate utilization and loss of respiratory control. Reversal of this type of swelling cannot be effected if the swelling change reaches a steady state. This type of swelling may provide cells with a mechanism for destroying mitochondrial substance.

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