title: Protein unfolding by the mitochondrial membrane potential.
abstract: Mitochondria can unfold importing precursor proteins by unraveling them from their N-termini. However, how this unraveling is induced is not known. Two candidates for the unfolding activity are the electrical potential across the inner mitochondrial membrane and mitochondrial Hsp70 in the matrix. Here, we propose that many precursors are unfolded by the electrical potential acting directly on positively charged amino acid side chains in the targeting sequences. Only precursor proteins with targeting sequences that are long enough to reach the matrix at the initial interaction with the import machinery are unfolded by mitochondrial Hsp70, and this unfolding occurs even in the absence of a membrane potential.
authors.affiliation: Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, Illinois 60208-3500, USA.
authors.forename: Shihai
authors.initials: S
authors.lastname: Huang
authors.forename: Kevin S
authors.initials: KS
authors.lastname: Ratliff
authors.forename: Andreas
authors.initials: A
authors.lastname: Matouschek
mesh_terms: D024361:Amino Acids, Basic / Q000737:chemistry / Q000378:metabolism; D001426:Bacterial Proteins / Q000494:pharmacology; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D011489:Protein Denaturation / Q000187:drug effects; D017510:Protein Folding; D011498:Protein Precursors / Q000737:chemistry* / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D018892:Proton-Motive Force / Q000187:drug effects; D012260:Ribonucleases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology; D055672:Static Electricity
chemical_list: D024361:Amino Acids, Basic; D001426:Bacterial Proteins; D018840:HSP70 Heat-Shock Proteins; D011498:Protein Precursors; C057438:barstar protein, Bacillus amyloliquefaciens; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D012260:Ribonucleases; C019760:Bacillus amyloliquefaciens ribonuclease