Failure to assemble the alpha 3 beta 3 subcomplex of the ATP synthase leads to accumulation of the alpha and beta subunits within inclusion bodies and the loss of mitochondrial cristae in Saccharomyces cerevisiae.
The F(1) component of mitochondrial ATP synthase is an oligomeric assembly of five different subunits, alpha, beta, gamma, delta, and epsilon. In terms of mass, the bulk of the structure ( approximately 90%) is provided by the alpha and beta subunits, which form an (alphabeta)(3) hexamer with adenine nucleotide binding sites at the alpha/beta interfaces. We report here ultrastructural and immunocytochemical analyses of yeast mutants that are unable to form the alpha(3)beta(3) oligomer, either because the alpha or the beta subunit is missing or because the cells are deficient for proteins that mediate F assembly (e.g. Atp11p, Atp12p, or Fmc1p). The F(1) alpha(1) and beta subunits of such mutant strains are detected within large electron-dense particles in the mitochondrial matrix. The composition of the aggregated species is principally full-length F(1) alpha and/or beta subunit protein that has been processed to remove the amino-terminal targeting peptide. To our knowledge this is the first demonstration of mitochondrial inclusion bodies that are formed largely of one particular protein species. We also show that yeast mutants lacking the alpha(3)beta(3) oligomer are devoid of mitochondrial cristae and are severely deficient for respiratory complexes III and IV. These observations are in accord with other studies in the literature that have pointed to a central role for the ATP synthase in biogenesis of the mitochondrial inner membrane.
Lefebvre-Legendre
Linnka
L
Institut de Biochimie et Génétique Cellulaires du Centre National de la Recherche Scientifique, Université Victor Segalen, 1 Rue Camille Saint-Saëns, Bordeaux 33077 Cedex, France.
Salin
Bénédicte
B
Schaëffer
Jacques
J
Brèthes
Daniel
D
Dautant
Alain
A
Ackerman
Sharon H
SH
di Rago
Jean-Paul
JP
D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000201:enzymology* / Q000235:genetics / Q000648:ultrastructure*; D008928:Mitochondria / Q000201:enzymology / Q000235:genetics / Q000648:ultrastructure*; D025261:Mitochondrial Proton-Translocating ATPases / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure*; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics / Q000648:ultrastructure*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure
D021122:Protein Subunits; D029701:Saccharomyces cerevisiae Proteins; D025261:Mitochondrial Proton-Translocating ATPases