Studies on the effect of toxin T-514 on the integrity of peroxisomes in methylotrophic yeasts

Abstract

We have studied the response of two methylotrophic yeasts (Hansenula polymorpha and Candida boidinii) to toxin T-514, a toxin lethal to man, extracted from the shrub Karwinska homboldtiana. Growth experiments indicated a dose-response effect; at enhanced concentrations (50 µg/ml) the different subcellular organelles rapidly disintegrated resulting in death of the cultures. At non-lethal concentrations (<2µg/ml) growth ceased initially, but resumed after a lag period of 4 h. At the subcellular level a specific effect was observed on peroxisomal integrity. Distinct holes appeared in the peroxisomal membranes, resulting in leakage of matrix proteins from these organelles. In addition, import of newly synthesized proteins appeared to be blocked since cytosolic aggregates of matrix proteins were formed. The peroxisomal damage was probably irreversible since affected organelles were degraded at later stages of incubation. Upon restoration of growth on methanol, new peroxisomes developed from those which had escaped degradation.