ausblenden:
Schlagwörter:
ATP-Dependent Proteases
Adenosine Triphosphate/metabolism
HSP40 Heat-Shock Proteins
HSP70 Heat-Shock Proteins/metabolism
Heat-Shock Proteins/genetics/metabolism
L-Lactate Dehydrogenase/genetics/metabolism
L-Lactate Dehydrogenase (Cytochrome)
Lactalbumin/genetics/metabolism
Membrane Proteins/metabolism
Mitochondria/*metabolism
Mitochondrial Proteins
Molecular Chaperones/*metabolism
*Protein Folding
Protein Sorting Signals/genetics/metabolism
Proton-Translocating ATPases/genetics/metabolism
*Protozoan Proteins
Recombinant Fusion Proteins/metabolism
Saccharomyces cerevisiae/*metabolism
*Saccharomyces cerevisiae Proteins
Sequence Homology, Amino Acid
Serine Endopeptidases/genetics/*metabolism
Tetrahydrofolate Dehydrogenase/genetics/metabolism
Zusammenfassung:
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.
