Biotin deficiency and the sparing effect of nordihydroguaiaretic acid in Neurospora crassa.

Abstract

The requirement of wild-type Neurospora crassa for biotin in growth and survival was examined. Extensional growth rates during biotin depletion were measured. With egg-white avidin to sequester trace biotin contamination in purified medium, the requirement was absolute. The presence of the free radical scavenger, nordihydroguaiaretic acid (NDGA), enhanced growth rate during either moderate or severe biotin limitation. Conidia did not undergo biotinless death, even in the presence of avidin. Apparently, endogenous biotin concentration was sufficient for survival. Since biotin is a cofactor for fatty acid synthesis and biotin deficiency depletes the cellular lipid content, the results of these experiments are consistent with the hypothesis that nutritional deficiencies in lipid and membrane synthesis leading to synthesis of abnormal membranes promote excessive lipid peroxidation and free radical damage and, consequently, cellular senescence. Inhibition of these processes by NDGA therefore enhances the cellular growth rate with limiting biotin.