AAA proteases with catalytic sites on opposite membrane surfaces comprise a proteolytic system for the ATP-dependent degradation of inner membrane proteins in mitochondria

EMBO J. 1996 Aug 15;15(16):4218-29.


The mechanism of selective protein degradation of membrane proteins in mitochondria has been studied employing a model protein that is subject to rapid proteolysis within the inner membrane. Protein degradation was mediated by two different proteases: (i) the m-AAA protease, a protease complex consisting of multiple copies of the ATP-dependent metallopeptidases Yta1Op (Afg3p) and Yta12p (Rcalp); and (ii) by Ymelp (Ytallp) that also is embedded in the inner membrane. Ymelp, highly homologous to Yta1Op and Yta12p, forms a complex of approximately 850 kDa in the inner membrane and exerts ATP-dependent metallopeptidase activity. While the m-AAA protease exposes catalytic sites to the mitochondrial matrix, Ymelp is active in the intermembrane space. The Ymelp complex was therefore termed 'i-AAA protease'. Analysis of the proteolytic fragments indicated cleavage of the model polypeptide at the inner and outer membrane surface and within the membrane-spanning domain. Thus, two AAA proteases with their catalytic sites on opposite membrane surfaces constitute a novel proteolytic system for the degradation of membrane proteins in mitochondria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Dependent Proteases
  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / metabolism*
  • Adenosine Triphosphate / physiology*
  • Binding Sites
  • Electron Transport Complex IV / metabolism
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • Intracellular Membranes / metabolism*
  • Membrane Proteins / metabolism*
  • Metalloendopeptidases*
  • Mitochondria / metabolism*
  • Mitochondria / ultrastructure
  • Mitochondrial Proteins
  • Mutagenesis, Site-Directed
  • Recombinant Fusion Proteins / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins*
  • Tetrahydrofolate Dehydrogenase / metabolism


  • Fungal Proteins
  • Membrane Proteins
  • Mitochondrial Proteins
  • Recombinant Fusion Proteins
  • Saccharomyces cerevisiae Proteins
  • Adenosine Triphosphate
  • Tetrahydrofolate Dehydrogenase
  • Electron Transport Complex IV
  • ATP-Dependent Proteases
  • YME1 protein, S cerevisiae
  • Metalloendopeptidases
  • Adenosine Triphosphatases
  • YTA12 protein, S cerevisiae
  • AFG3 protein, S cerevisiae