The Protein Import Motor of Mitochondria: Unfolding and Trapping of Preproteins Are Distinct and Separable Functions of Matrix Hsp70

• Published in: Cell 1999-05, Vol.97 (5), p.565-574
• Main Authors: Voisine, Cindy, Craig, Elizabeth A, Zufall, Nicole, von Ahsen, Oliver, Pfanner, Nikolaus, Voos, Wolfgang
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphate - metabolism; Calcium-Transporting ATPases; Fungal Proteins - chemistry; Fungal Proteins - metabolism; HSP70 Heat-Shock Proteins - metabolism; Kinetics; Mitochondria - metabolism; Models, Molecular; Molecular Chaperones - chemistry; Molecular Chaperones - genetics; Molecular Chaperones - metabolism; Protein Folding; Protein Precursors - chemistry; Protein Precursors - metabolism; Protein Structure, Secondary; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins; Suppression, Genetic; Tetrahydrofolate Dehydrogenase - chemistry; Tetrahydrofolate Dehydrogenase - metabolism; Valinomycin - pharmacology
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/S0092-8674(00)80768-0

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.