Mutant residues suppressing ρ 0-lethality in Kluyveromyces lactis occur at contact sites between subunits of F 1-ATPase

Abstract

Characterisation of 35 Kluyveromyces lactis strains lacking mitochondrial DNA has shown that mutations suppressing ρ 0-lethality are limited to the ATP1, 2 and 3 genes coding for the α-, β- and γ- subunits of mitochondrial F 1-ATPase. All atp mutations reduce growth on glucose and three alleles, atp1-2, 1-3 and atp3-1, produce a respiratory deficient phenotype that indicates a drop in efficiency of the F 1F 0-ATP synthase complex. ATPase activity is needed for suppression as a double mutant containing an atp allele, together with a mutation abolishing catalytic activity, does not suppress ρ 0-lethality. Positioning of the seven amino acids subject to mutation on the bovine F 1-ATPase structure shows that two residues are found in a membrane proximal region while five amino acids occur at a region suggested to be a molecular bearing. The intriguing juxtaposition of mutable amino acids to other residues subject to change suggests that mutations affect subunit interactions and alter the properties of F 1 in a manner yet to be determined. An explanation for suppressor activity of atp mutations is discussed in the context of a possible role for F 1-ATPase in the maintenance of mitochondrial inner membrane potential.