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キーワード:
ATP-Dependent Proteases
Adenosine Triphosphate/*pharmacology
Animals
Cattle
Cholesterol Side-Chain Cleavage Enzyme/*metabolism
Fungal Proteins/physiology
Fungi/*physiology
HSP70 Heat-Shock Proteins/*physiology
Heat-Shock Proteins/metabolism
Mitochondria/*metabolism/microbiology
Mitochondrial Proteins
Molecular Chaperones/physiology
Recombinant Fusion Proteins/metabolism
*Saccharomyces cerevisiae Proteins
Serine Endopeptidases/*metabolism
Substrate Specificity
要旨:
To analyze protein degradation in mitochondria and the role of molecular chaperone proteins in this process, bovine apocytochrome P450scc was employed as a model protein. When imported into isolated yeast mitochondria, P450scc was mislocalized to the matrix and rapidly degraded. This proteolytic breakdown was mediated by the ATP-dependent PIM1 protease, a Lon-like protease in the mitochondrial matrix, in cooperation with the mtHsp70 system. In addition, a derivative of P450scc was studied to which a heterologous transmembrane region was fused at the amino terminus. This protein became anchored to the inner membrane upon import and was degraded by the membrane-embedded, ATP-dependent m-AAA protease. Again, degradation depended on the mtHsp70 system; it was inhibited at non-permissive temperature in mitochondria carrying temperature-sensitive mutant forms of Ssc1p, Mdj1p, or Mge1p. These results demonstrate overlapping substrate specificities of PIM1 and the m-AAA protease, and they assign a central role to the mtHsp70 system during the degradation of misfolded polypeptides by both proteases.
