title: The disaggregation activity of the mitochondrial ClpB homolog Hsp78 maintains Hsp70 function during heat stress.
abstract: Molecular chaperones are important components of mitochondrial protein biogenesis and are required to maintain the organellar function under normal and stress conditions. We addressed the functional role of the Hsp100/ClpB homolog Hsp78 during aggregation reactions and its functional cooperation with the main mitochondrial Hsp70, Ssc1, in mitochondria of the yeast Saccharomyces cerevisiae. By establishing an aggregation/disaggregation assay in intact mitochondria we demonstrated that Hsp78 is indispensable for the resolubilization of protein aggregates generated by heat stress under in vivo conditions. The ATP-dependent disaggregation activity of Hsp78 was capable of reversing the preprotein import defect of a destabilized mutant form of Ssc1. This role in disaggregation of Ssc1 is unique for Hsp78, since the recently identified, Hsp70-specific chaperone Zim17 had no effect on the resolubilization reaction. We observed only a minor effect of the second mitochondrial Hsp100 family member Mcx1 on protein disaggregation. A "holding" activity of the mitochondrial Hsp70 system was a prerequisite for a successful resolubilization of aggregated proteins. We conclude that the protective role of Hsp78 in thermotolerance is mainly based on maintaining the molecular chaperone Ssc1 in a soluble and functional state.
authors.affiliation: Institut für Biochemie und Molekularbiologie, Hermann-Herder-Str. 7, Universität Freiburg, 79104 Freiburg, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: von Janowsky
authors.forename: Tamara
authors.initials: T
authors.lastname: Major
authors.forename: Karin
authors.initials: K
authors.lastname: Knapp
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Voos
mesh_terms: D049069:ATP-Dependent Proteases; D000252:Calcium-Transporting ATPases / Q000235:genetics / Q000502:physiology; D049071:Endopeptidase Clp / Q000737:chemistry* / Q000235:genetics; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000502:physiology*; D006360:Heat-Shock Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D006358:Hot Temperature; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000502:physiology; D018832:Molecular Chaperones / Q000235:genetics / Q000502:physiology; D009154:Mutation; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D012697:Serine Endopeptidases / Q000502:physiology; D012995:Solubility
chemical_list: D018840:HSP70 Heat-Shock Proteins; C083349:HSP78 protein, S cerevisiae; D006360:Heat-Shock Proteins; C115923:Mcx1 protein, S cerevisiae; D024101:Mitochondrial Proteins; D018832:Molecular Chaperones; C101767:SSC1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C495990:Zim17 protein, S cerevisiae; D049069:ATP-Dependent Proteases; C085155:PIM1 protein, S cerevisiae; D012697:Serine Endopeptidases; D049071:Endopeptidase Clp; D000252:Calcium-Transporting ATPases