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

• Published in: Biochimica et biophysica acta Vol. 1478; no. 1; p. 125
• Main Authors: Clark-Walker, G D, Hansbro, P M, Gibson, F, Chen, X J
• Format: Journal Article
• Language: English
• Published: Netherlands 16.03.2000
• Subjects: Alleles; Crystallography; Genes, Lethal; Genes, Suppressor; Genotype; Kluyveromyces - enzymology; Kluyveromyces - genetics; Kluyveromyces - growth & development; Mitochondria - enzymology; Models, Molecular; Mutation; Proton-Translocating ATPases - chemistry; Proton-Translocating ATPases - genetics
• ISSN: 0006-3002
• DOI: 10.1016/s0167-4838(00)00003-0

Characterisation of 35 Kluyveromyces lactis strains lacking mitochondrial DNA has shown that mutations suppressing rho(0)-lethality are limited to the ATP1, 2 and 3 genes coding for the alpha-, beta- and gamma- 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(1)F(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 rho(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.