The m-AAA protease processes cytochrome c peroxidase preferentially at the inner boundary membrane of mitochondria

Mol Biol Cell. 2009 Jan;20(2):572-80. doi: 10.1091/mbc.e07-11-1112. Epub 2008 Nov 19.

Abstract

The m-AAA protease is a conserved hetero-oligomeric complex in the inner membrane of mitochondria. Recent evidence suggests a compartmentalization of the contiguous mitochondrial inner membrane into an inner boundary membrane (IBM) and a cristae membrane (CM). However, little is known about the functional differences of these subdomains. We have analyzed the localizations of the m-AAA protease and its substrate cytochrome c peroxidase (Ccp1) within yeast mitochondria using live cell fluorescence microscopy and quantitative immunoelectron microscopy. We find that the m-AAA protease is preferentially localized in the IBM. Likewise, the membrane-anchored precursor form of Ccp1 accumulates in the IBM of mitochondria lacking a functional m-AAA protease. Only upon proteolytic cleavage the mature form mCcp1 moves into the cristae space. These findings suggest that protein quality control and proteolytic activation exerted by the m-AAA protease take place preferentially in the IBM pointing to significant functional differences between the IBM and the CM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / metabolism*
  • Animals
  • Cytochrome-c Peroxidase / genetics
  • Cytochrome-c Peroxidase / metabolism*
  • Humans
  • Metalloendopeptidases / genetics
  • Metalloendopeptidases / metabolism*
  • Mitochondria / enzymology
  • Mitochondria / ultrastructure
  • Mitochondrial Membranes / enzymology*
  • Mitochondrial Membranes / ultrastructure
  • Mitochondrial Proteins
  • Protein Precursors / genetics
  • Protein Precursors / metabolism
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*

Substances

  • Mitochondrial Proteins
  • Protein Precursors
  • Protein Subunits
  • Recombinant Fusion Proteins
  • Saccharomyces cerevisiae Proteins
  • Cytochrome-c Peroxidase
  • Metalloendopeptidases
  • m-AAA proteases
  • Adenosine Triphosphatases
  • YTA12 protein, S cerevisiae
  • AFG3 protein, S cerevisiae