The formation of respiratory chain complexes in mitochondria is under the proteolytic control of the m-AAA protease.
Yta10p (Afg3p) and Yta12p (Rcal1p), members of the conserved AAA family of ATPases, are subunits of the mitochondrial m-AAA protease, an inner membrane ATP-dependent metallopeptidase. Deletion of YTA10 or YTA12 impairs degradation of non-assembled inner membrane proteins and assembly of respiratory chain complexes. Mutations of the proteolytic sites in either YTA10 or YTA12 have been shown to inhibit proteolysis of membrane-integrated polypeptides but not the respiratory competence of the cells, suggesting additional activities of Yta10p and Yta12p. Here we demonstrate essential proteolytic functions of the m-AAA protease in the biogenesis of the respiratory chain. Cells harbouring proteolytically inactive forms of both Yta10p and Yta12p are respiratory deficient and exhibit a pleiotropic phenotype similar to Deltayta10 and Deltayta12 cells. They show deficiencies in expression of the intron-containing mitochondrial genes COX1 and COB. Splicing of COX1 and COB transcripts is impaired in mitochondria lacking m-AAA protease, whilst transcription and translation can proceed in the absence of Yta10p or Yta12p. The function of the m-AAA protease appears to be confined to introns encoding mRNA maturases. Our results reveal an overlapping substrate specificity of the subunits of the m-AAA protease and explain the impaired assembly of respiratory chain complexes by defects in expression of intron-containing genes in mitochondria lacking m-AAA protease.
Institut für Physiologische Chemie der Universität München, Goethestrasse 33, 80336 München, Germany.
H
H
Arlt
G
G
Steglich
R
R
Perryman
B
B
Guiard
W
W
Neupert
T
T
Langer
D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D051545:Cyclooxygenase 1; D004579:Electron Transport; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D006868:Hydrolysis; D007438:Introns; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008666:Metalloendopeptidases / Q000235:genetics; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism*; D009154:Mutation; D010641:Phenotype; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism; D011480:Protease Inhibitors; D011499:Protein Processing, Post-Translational; D012326:RNA Splicing; D029701:Saccharomyces cerevisiae Proteins; D013379:Substrate Specificity
D005656:Fungal Proteins; D007527:Isoenzymes; D011480:Protease Inhibitors; D029701:Saccharomyces cerevisiae Proteins; D051545:Cyclooxygenase 1; D011451:Prostaglandin-Endoperoxide Synthases; D003576:Electron Transport Complex IV; D008666:Metalloendopeptidases; C114583:m-AAA proteases; D000251:Adenosine Triphosphatases; C090045:AFG3 protein, S cerevisiae