Membrane protein turnover by the m-AAA protease in mitochondria depends on the transmembrane domains of its subunits.
AAA proteases are membrane-bound ATP-dependent proteases that are present in eubacteria, mitochondria and chloroplasts and that can degrade membrane proteins. Recent evidence suggests dislocation of membrane-embedded substrates for proteolysis to occur in a hydrophilic environment; however, next to nothing is known about the mechanism of this process. Here, we have analysed the role of the membrane-spanning domains of Yta10 and Yta12, which are conserved subunits of the hetero-oligomeric m-AAA protease in the mitochondria of Saccharomyces cerevisiae. We demonstrate that the m-AAA protease retains proteolytic activity after deletion of the transmembrane segments of either Yta10 or Yta12. Although the mutant m-AAA protease is still capable of processing cytochrome c peroxidase and degrading a peripheral membrane protein, proteolysis of integral membrane proteins is impaired. We therefore propose that transmembrane segments of m-AAA protease subunits have a direct role in the dislocation of membrane-embedded substrates.
Item Type | Article |
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Keywords | Adenosine Triphosphatases/physiology, Adenosine Triphosphate/metabolism, Cell Membrane/ metabolism, Cell Proliferation, Cytochrome-c Peroxidase/metabolism, Electrophoresis, Polyacrylamide Gel, Gene Deletion, Immunoprecipitation, Metalloendopeptidases/metabolism/ physiology, Mitochondria/ metabolism, Mutagenesis, Oxygen Consumption, Protein Conformation, Protein Structure, Tertiary, Saccharomyces cerevisiae/metabolism, Saccharomyces cerevisiae Proteins/physiology, Temperature, Time Factors, Adenosine Triphosphatases, physiology, Adenosine Triphosphate, metabolism, Cell Membrane, metabolism, Cell Proliferation, Cytochrome-c Peroxidase, metabolism, Electrophoresis, Polyacrylamide Gel, Gene Deletion, Immunoprecipitation, Metalloendopeptidases, metabolism, physiology, Mitochondria, metabolism, Mutagenesis, Oxygen Consumption, Protein Conformation, Protein Structure, Tertiary, Saccharomyces cerevisiae, metabolism, Saccharomyces cerevisiae Proteins, physiology, Temperature, Time Factors |
ISI | 223005100012 |