Effects of hap mutations on heme and cytochrome formation in yeast

Simultaneous effects of mutations in the transcriptional regulatory genes, HAP1, HAP2 and HAP3, on all respiratory cytochromes of Saccharomyces cerevisiae were determined. Cytochrome behavior in hap mutants and in cyc4 and rhm1 mutants, altered in regulation of 5-aminolevulinate synthase, was compared. Although hap mutants were isolated as trans-acting, transcriptional regulators of the CYC1 (iso-1-cytochrome c) gene, each mutant exhibits partial deficiencies in all cytochrome types. In hap2 and hap3 strains all cytochromes were decreased proportionally to about 40-50% of wild type values. In contrast, hap1 caused a decrease in all cytochromes and an accumulation of a pigment, probably Zn porphyrin. Apparently apocytochrome and heme biosynthesis retain coordination in hap2 and hap3, but not in hap1, mutants. Unlike cyc4 and rhm1 mutants, hap mutants do not exhibit 5-aminolevulinate-dependent restoration of cytochromes. The hap1 mutant grew at near-normal rates on glycerol, whereas hap2 and hap3 mutants grew very slowly. The frequency of [rho-] was high (16-18%) in hap2 and hap3 strains. Results are consistent with generalized control of mitochondrial replication directed by the HAP1-HAP2 system and heme-directed control of formation of all apocytochromes mediated by HAP1. Neither system exerts all-or-nothing control.