Genetic and biochemical basis for viability of yeast lacking mitochondrial genomes.
Yme1p, an ATP-dependent protease localized in the mitochondrial inner membrane, is required for the growth of yeast lacking an intact mitochondrial genome. Specific dominant mutations in the genes encoding the alpha- and gamma-subunits of the mitochondrial F(1)F(0)-ATPase suppress the slow-growth phenotype of yeast that simultaneously lack Yme1p and mitochondrial DNA. F(1)F(0)-ATPase activity is reduced in yeast lacking Yme1p and is restored in yme1 strains bearing suppressing mutations in F(1)-ATPase structural genes. Mitochondria isolated from yme1 yeast generated a membrane potential upon the addition of succinate, but unlike mitochondria isolated either from wild-type yeast or from yeast bearing yme1 and a suppressing mutation, were unable to generate a membrane potential upon the addition of ATP. Nuclear-encoded F(0) subunits accumulate in yme1 yeast lacking mitochondrial DNA; however, deletion of genes encoding those subunits did not suppress the requirement of yme1 yeast for intact mitochondrial DNA. In contrast, deletion of INH1, which encodes an inhibitor of the F(1)F(0)-ATPase, partially suppressed the growth defect of yme1 yeast lacking mitochondrial DNA. We conclude that Yme1p is in part responsible for assuring sufficient F(1)F(0)-ATPase activity to generate a membrane potential in mitochondria lacking mitochondrial DNA and propose that Yme1p accomplishes this by catalyzing the turnover of protein inhibitors of the F(1)F(0)-ATPase.
Kominsky
Douglas J
DJ
Department of Molecular Biology, University of Wyoming, Laramie, Wyoming 82071, USA.
Brownson
Mary P
MP
Updike
Dustin L
DL
Thorsness
Peter E
PE
D049069:ATP-Dependent Proteases; D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D004271:DNA, Fungal / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics*; D017353:Gene Deletion; D016681:Genome, Fungal; D008564:Membrane Potentials; D008928:Mitochondria / Q000378:metabolism; D010641:Phenotype; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism
D004271:DNA, Fungal; D004272:DNA, Mitochondrial; D029701:Saccharomyces cerevisiae Proteins; D049069:ATP-Dependent Proteases; C082702:YME1 protein, S cerevisiae; D000251:Adenosine Triphosphatases; D006180:Proton-Translocating ATPases