title: The protein import motor of mitochondria: unfolding and trapping of preproteins are distinct and separable functions of matrix Hsp70.
abstract: Mitochondrial heat shock protein 70 (mtHsp70) functions in unfolding, translocation, and folding of imported proteins. Controversial models of mtHsp70 action have been discussed: (1) physical trapping of preproteins is sufficient to explain the various mtHsp70 functions, and (2) unfolding of preproteins requires an active motor function of mtHsp70 ("pulling"). Intragenic suppressors of a mutant mtHsp70 separate two functions: a nonlethal folding defect caused by enhanced trapping of preproteins, and a conditionally lethal unfolding defect caused by an impaired interaction of mtHsp70 with the membrane anchor Tim44. Even enhanced trapping in wild-type mitochondria does not generate a pulling force. The motor function of mtHsp70 cannot be explained by passive trapping alone but includes an essential ATP-dependent interaction with Tim44 to generate a pulling force and unfold preproteins.
authors.affiliation: Department of Biomolecular Chemistry, University of Wisconsin-Madison, 53706, USA.
authors.forename: C
authors.initials: C
authors.lastname: Voisine
authors.forename: E A
authors.initials: EA
authors.lastname: Craig
authors.forename: N
authors.initials: N
authors.lastname: Zufall
authors.forename: O
authors.initials: O
authors.lastname: von Ahsen
authors.forename: N
authors.initials: N
authors.lastname: Pfanner
authors.forename: W
authors.initials: W
authors.lastname: Voos
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000252:Calcium-Transporting ATPases; D005656:Fungal Proteins / Q000737:chemistry / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D007700:Kinetics; D008928:Mitochondria / Q000378:metabolism*; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017510:Protein Folding; D011498:Protein Precursors / Q000737:chemistry / Q000378:metabolism*; D017433:Protein Structure, Secondary; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D013489:Suppression, Genetic; D013762:Tetrahydrofolate Dehydrogenase / Q000737:chemistry / Q000378:metabolism; D014634:Valinomycin / Q000494:pharmacology
chemical_list: D005656:Fungal Proteins; D018840:HSP70 Heat-Shock Proteins; D018832:Molecular Chaperones; D011498:Protein Precursors; C101767:SSC1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014634:Valinomycin; D000255:Adenosine Triphosphate; D013762:Tetrahydrofolate Dehydrogenase; D000252:Calcium-Transporting ATPases