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PMID: 7957078 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Molecular chaperones cooperate with PIM1 protease in the degradation of misfolded proteins in mitochondria.

The EMBO journal ·Vol. 13 ·No. 21 ·1994-11-01 ·Pages 5135-45

Wagner I, Arlt H, van Dyck L, Langer T, Neupert W

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.

MeSH Terms
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
Chemicals
HSP40 Heat-Shock Proteins HSP70 Heat-Shock Proteins Heat-Shock Proteins MDJ1 protein, S cerevisiae Membrane Proteins Mitochondrial Proteins Molecular Chaperones Protein Sorting Signals Protozoan Proteins Recombinant Fusion Proteins Saccharomyces cerevisiae Proteins mtp70 protein, Trypanosoma cruzi Adenosine Triphosphate Lactalbumin L-Lactate Dehydrogenase L-Lactate Dehydrogenase (Cytochrome) Tetrahydrofolate Dehydrogenase ATP-Dependent Proteases PIM1 protein, S cerevisiae Serine Endopeptidases Proton-Translocating ATPases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Wagner I
Institut für Physiologische Chemie, Universität München, Germany.
Arlt H
van Dyck L
Langer T
Neupert W
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1994-11-01
Pages
5135-45
Language
English
Region
England
NLM ID
8208664
PMCID
PMC395461
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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