Genetic and Biochemical Basis for Viability of Yeast Lacking Mitochondrial Genomes

Corresponding author: Peter E. Thorsness, University of Wyoming, Laramie, WY 82071-3944., thorsnes{at}uwyo.edu (E-mail)

Communicating editor: A. P. MITCHELL

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 - and -subunits of the mitochondrial F₁F₀-ATPase suppress the slow-growth phenotype of yeast that simultaneously lack Yme1p and mitochondrial DNA. F₁F₀-ATPase activity is reduced in yeast lacking Yme1p and is restored in yme1 strains bearing suppressing mutations in F₁-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 F₀ 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 F₁F₀-ATPase, partially suppressed the growth defect of yme1 yeast lacking mitochondrial DNA. We conclude that Yme1p is in part responsible for assuring sufficient F₁F₀-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 F₁F₀-ATPase.

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