Quantitation of effects on mitochondrial swelling: some effects of ATP and aging

¹ Medical Research Programs, Veterans Administration Hospital, Long Beach, California

A method has been devised for the quantitative measurement of relative effects of substances or conditions on rate of change of mitochondrial volume. It can be used to study the effects progressively as the mitochondria swell. By this means, the effects of adenosine triphosphate (ATP) and aging on mitochondrial swelling were investigated. It was found that at constant mitochondrial volume, the rate of change of volume is a logarithmic function of aging time. The swelling of fresh mitochondria was mildly inhibited by ATP at very low volumes. Aging of rat liver mitochondria caused this inhibitory effect to be replaced by enhancement of swelling, which became greater in magnitude and was retained through larger volumes as aging time increased. The swelling enhancement was followed by inhibition, the magnitude of which increased with further swelling. The inhibitory effect of ATP on swelling of mouse liver mitochondria underwent a sudden marked increase at a particular mitochondrial volume independent of aging time and time of ATP exposure. At lower volumes the effect of ATP increased with aging time and swelling rate, whereas at larger volumes this relation ceased to be apparent. The possible significance of these results is discussed.