Factors affecting the inhibition by alloxan,and effect of streptozotocin on phosphate transport in isolated mouse mitochondria

Summary The swelling technique evidenced inhibition of P_i transport in isolated mouse liver mitochondria by 1 mM or higher concentration of alloxan, while no effect was found with streptozotocin. Complete or partial protection against alloxan inhibition was found under the following conditions: preincubation at 4 °C, or pretreatment with P_i, glucagon, succinate, malate or pyruvate. Complete protection was observed in isolated mitochondria from mice injected with glucagon. No protection was seen under the following conditions: preincubation at 37 °C, addition of microsomes, or pretreatment with insulin or glucagon in the presence of glucagon antibodies. So-called light and heavy mitochondria were as sensitive to alloxan as those obtained with the routine technique. Alloxanic acid had no effect, and addition of cysteine or glutathione abolished the inhibition by alloxan. Alloxan inhibited P_i transport also in isolated lung mitochondria. The findings suggest a direct action of alloxan on mitochondrial P_i transport which is affected by the energetic state. A relationship seems to exist between protection against alloxan toxicityin vivo and protection under the present experimental conditions.