title: The mitochondrial chaperonin hsp60 is required for its own assembly.
abstract: Heatshock protein 60 (hsp60) in the matrix of mitochondria is essential for the folding and assembly of newly imported proteins. Hsp60 belongs to a class of structurally related chaperonins found in organelles of endosymbiotic origin and in the bacterial cytosol. Hsp60 monomers form a complex arranged as two stacked 7-mer rings. This 14-mer complex binds unfolded proteins at its surface, then seems to catalyse their folding in an ATP-dependent process. The question arises as to how such an assembly machinery is itself folded and assembled. Hsp60 subunits are encoded by a nuclear gene and translated in the cytosol as precursors which are translocated into mitochondria and proteolytically processed. In both intact cells and isolated mitochondria of the hsp60-defective yeast mutant mif4, self-assembly of newly imported wild-type subunits is not observed. Functional pre-existing hsp60 complex is required in order to form new, assembled, 14-mer. Subunits imported in vitro are assembled with a surprisingly fast half-time of 5-10 min, indicative of a catalysed reaction. These findings are further evidence that self-assembly may not be the principal mechanism by which proteins attain their functional conformation in the intact cell.
authors.affiliation: Howard Hughes Medical Institute, Department of Human Genetics, Yale School of Medicine, New Haven, Connecticut 06510.
authors.forename: M Y
authors.initials: MY
authors.lastname: Cheng
authors.forename: F U
authors.initials: FU
authors.lastname: Hartl
authors.forename: A L
authors.initials: AL
authors.lastname: Horwich
mesh_terms: D001692:Biological Transport; D018834:Chaperonin 60; D018833:Chaperonins; D004591:Electrophoresis, Polyacrylamide Gel; D005656:Fungal Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000502:physiology*; D046911:Macromolecular Substances; D008928:Mitochondria / Q000378:metabolism*; D008970:Molecular Weight; D011487:Protein Conformation; D011498:Protein Precursors / Q000378:metabolism; D011506:Proteins / Q000502:physiology*; D012441:Saccharomyces cerevisiae
chemical_list: D018834:Chaperonin 60; D005656:Fungal Proteins; D006360:Heat-Shock Proteins; D046911:Macromolecular Substances; D011498:Protein Precursors; D011506:Proteins; D018833:Chaperonins