QSR1, an essential yeast gene with a genetic relationship to a subunit of the mitochondrial cytochrome bc1 complex, is homologous to a gene implicated in eukaryotic cell differentiation

Abstract

Subunit 6 of the mitochondrial cytochrome bc1 complex regulates the activity of the bc1 complex in Saccharomyces cerevisiae but is not essential for respiration. To test whether QCR6, the nuclear gene which encodes subunit 6, might be functionally redundant with any other gene(s), we screened for mutations in yeast genes which are essential when the otherwise non-essential QCR6 is deleted from the yeast chromosome. We obtained such quinolcytochrome c reductase subunit-requiring mutants in two complementation groups, which we named qsr1 and qsr2. The qsr mutants require QCR6 for viability on fermentable and non-fermentable carbon sources, indicating that QCR6 is covering lethal mutations in qsr1 and qsr2, even when the yeast do not require respiration. QSR1 was cloned by rescuing the synthetic lethality of a qsr1-1 mutant. QSR1 encodes a 25.4-kDa protein which is 65% identical to a protein encoded by QM, a highly conserved human gene which has been implicated in tumorigenesis. In mammals QM is down-regulated during adipocyte, kidney, and heart differentiation, and in Nicotiana the homolog of QM is also down-regulated during differentiation. When one chromosomal copy of QSR1 was deleted in a diploid yeast strain, haploid spores derived therefrom and carrying the deletion were unable to grow on fermentable or non-fermentable carbon sources. Although QCR6 allows the qsr1-1 mutant to grow, it will not substitute for QSR1, since the deletion of QSR1 is lethal even if QCR6 is present. These results indicate a novel genetic relationship between a subunit of the mitochondrial respiratory chain and an essential gene in yeast which is homologous to a gene implicated in differentiation in other eukaryotes.