The protein import motor of mitochondria: unfolding and trapping of preproteins are distinct and separable functions of matrix Hsp70.
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.
Voisine
C
C
Department of Biomolecular Chemistry, University of Wisconsin-Madison, 53706, USA.
Craig
E A
EA
Zufall
N
N
von Ahsen
O
O
Pfanner
N
N
Voos
W
W
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
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