Dual Mutations Reveal Interactions Between Components of Oxidative Phosphorylation in Kluyveromyces lactis

Corresponding author: G. D. Clark-Walker, Molecular Genetics and Evolution Group, Research School of Biological Sciences, The Australian National University, PO Box 475, Canberra, ACT, 2601, Australia., dcw{at}rsbs.anu.edu.au (E-mail)

Communicating editor: B. J. ANDREWS

Loss of mtDNA or mitochondrial protein synthesis cannot be tolerated by wild-type Kluyveromyces lactis. The mitochondrial function responsible for ⁰-lethality has been identified by disruption of nuclear genes encoding electron transport and F₀-ATP synthase components of oxidative phosphorylation. Sporulation of diploid strains heterozygous for disruptions in genes for the two components of oxidative phosphorylation results in the formation of nonviable spores inferred to contain both disruptions. Lethality of spores is thought to result from absence of a transmembrane potential, , across the mitochondrial inner membrane due to lack of proton pumping by the electron transport chain or reversal of F₁F₀-ATP synthase. Synergistic lethality, caused by disruption of nuclear genes, or ⁰-lethality can be suppressed by the atp2.1 mutation in the ß-subunit of F₁-ATPase. Suppression is viewed as occurring by an increased hydrolysis of ATP by mutant F₁, allowing sufficient electrogenic exchange by the translocase of ADP in the matrix for ATP in the cytosol to maintain . In addition, lethality of haploid strains with a disruption of AAC encoding the ADP/ATP translocase can be suppressed by atp2.1. In this case suppression is considered to occur by mutant F₁ acting in the forward direction to partially uncouple ATP production, thereby stimulating respiration and relieving detrimental hyperpolarization of the inner membrane. Participation of the ADP/ATP translocase in suppression of ⁰-lethality is supported by the observation that disruption of AAC abolishes suppressor activity of atp2.1.

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