Specific mutations in alpha- and gamma-subunits of F1-ATPase affect mitochondrial genome integrity in the petite-negative yeast Kluyveromyces lactis
Chen, X.J.; Clark-Walker, G.D.
EMBO Journal 14(13): 3277-3286
1995
ISSN/ISBN: 0261-4189 PMID: 7621839 Document Number: 452056
We have shown previously that mutations in nuclear genes, termed MGI, for mitochondrial genome integrity, can convert the petite-negative yeast Kluyveromyces lactis into a petite-positive form with the ability to produce mitochondrial genome deletion mutants (Chen and Clark-Walker, Genetics, 133, 517525, 1993). Here we describe that two genes, MG12 and MG15, encode the alpha- and gamma-subunits of mitochondrial F-1-ATPase. Specific mutations, Phe443 fwdarw Ser and Ala333 fwdarw Val in MG12, and Thr275 fwdarw Ala in MG15, confer on cells the ability to produce petite mutants spontaneously with deletions in mitochondrial (mt) DNA and the capacity to lose their mitochondrial genomes upon treatment with ethidium bromide. Structural integrity of the F-1 complex seems to be needed for expression of the Mgi- phenotype as null mutations in MGI2 and MGI5 remove the ability to form mtDNA deletions. It is suggested that mgi mutations allow petites to survive because an aberrant F-1 complex prevents collapse of the mitochondrial inner membrane potential that normally occurs on loss of mtDNA-encoded F-o subunits.