Abstract
ATP dependent proteolytic degradation of misfolded proteins in the mitochondrial matrix is mediated by the PIM1 protease and depends on the molecular chaperone proteins mt-hsp70 and Mdj1p. Chaperone function is essential to maintain misfolded proteins in a soluble state, a prerequisite for their degradation by PIM1 protease. In the absence of functional mt-hsp70 or Mdj1p misfolded proteins either remain associated with mt-hsp70 or form aggregates and thereby are no longer substrates for PIM1 protease. Mdj1p is shown to regulate the ATP dependent association of an unfolded polypeptide chain with mt-hsp70 affecting binding to as well as release from mt-hsp70. These findings establish a central role of molecular chaperone proteins in the degradation of misfolded proteins by PIM1 protease and thereby demonstrate a functional interrelation between components of the folding machinery and the proteolytic system within mitochondria.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP-Dependent Proteases
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Adenosine Triphosphate / metabolism
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HSP40 Heat-Shock Proteins
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HSP70 Heat-Shock Proteins / metabolism
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Heat-Shock Proteins / genetics
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Heat-Shock Proteins / metabolism
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L-Lactate Dehydrogenase (Cytochrome)
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L-Lactate Dehydrogenase / genetics
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L-Lactate Dehydrogenase / metabolism
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Lactalbumin / genetics
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Lactalbumin / metabolism
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Membrane Proteins / metabolism
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Mitochondria / metabolism*
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Mitochondrial Proteins
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Molecular Chaperones / metabolism*
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Protein Folding*
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Protein Sorting Signals / genetics
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Protein Sorting Signals / metabolism
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Proton-Translocating ATPases / genetics
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Proton-Translocating ATPases / metabolism
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Protozoan Proteins*
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Recombinant Fusion Proteins / metabolism
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Saccharomyces cerevisiae / metabolism*
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Saccharomyces cerevisiae Proteins*
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Sequence Homology, Amino Acid
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Serine Endopeptidases / genetics
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Serine Endopeptidases / metabolism*
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Tetrahydrofolate Dehydrogenase / genetics
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Tetrahydrofolate Dehydrogenase / metabolism
Substances
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HSP40 Heat-Shock Proteins
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HSP70 Heat-Shock Proteins
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Heat-Shock Proteins
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MDJ1 protein, S cerevisiae
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Membrane Proteins
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Mitochondrial Proteins
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Molecular Chaperones
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Protein Sorting Signals
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Protozoan Proteins
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Recombinant Fusion Proteins
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Saccharomyces cerevisiae Proteins
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mtp70 protein, Trypanosoma cruzi
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Adenosine Triphosphate
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Lactalbumin
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L-Lactate Dehydrogenase
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L-Lactate Dehydrogenase (Cytochrome)
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Tetrahydrofolate Dehydrogenase
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ATP-Dependent Proteases
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PIM1 protein, S cerevisiae
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Serine Endopeptidases
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Proton-Translocating ATPases