title: Prohibitins act as a membrane-bound chaperone for the stabilization of mitochondrial proteins.
abstract: Prohibitins are ubiquitous, abundant and evolutionarily strongly conserved proteins that play a role in important cellular processes. Using blue native electrophoresis we have demonstrated that human prohibitin and Bap37 together form a large complex in the mitochondrial inner membrane. This complex is similar in size to the yeast complex formed by the homologues Phb1p and Phb2p. In yeast, levels of this complex are increased on co-overexpression of both Phb1p and Phb2p, suggesting that these two proteins are the only components of the complex. Pulse-chase experiments with mitochondria isolated from phb1/phb2-null and PHB1/2 overexpressing cells show that the Phb1/2 complex is able to stabilize newly synthesized mitochondrial translation products. This stabilization probably occurs through a direct interaction because association of mitochondrial translation products with the Phb1/2 complex could be demonstrated. The fact that Phb1/2 is a large multimeric complex, which provides protection of native peptides against proteolysis, suggests a functional homology with protein chaperones with respect to their ability to hold and prevent misfolding of newly synthesized proteins.
authors.affiliation: Section for Molecular Biology and Department of Mass Spectrometry, Swammerdam Institute for Life Science, University of Amsterdam, Kruislaan 318, 1098 SM Amsterdam, The Netherlands. nijtmans@bio.uva.nl
authors.forename: L G
authors.initials: LG
authors.lastname: Nijtmans
authors.forename: L
authors.initials: L
authors.lastname: de Jong
authors.forename: M
authors.initials: M
authors.lastname: Artal Sanz
authors.forename: P J
authors.initials: PJ
authors.lastname: Coates
authors.forename: J A
authors.initials: JA
authors.lastname: Berden
authors.forename: J W
authors.initials: JW
authors.lastname: Back
authors.forename: A O
authors.initials: AO
authors.lastname: Muijsers
authors.forename: H
authors.initials: H
authors.lastname: van der Spek
authors.forename: L A
authors.initials: LA
authors.lastname: Grivell
mesh_terms: D000595:Amino Acid Sequence; D005656:Fungal Proteins / Q000502:physiology; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism*; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D018832:Molecular Chaperones / Q000502:physiology*; D008969:Molecular Sequence Data; D000091402:Prohibitins; D017510:Protein Folding; D011506:Proteins / Q000378:metabolism / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D005656:Fungal Proteins; D046911:Macromolecular Substances; D008565:Membrane Proteins; D018832:Molecular Chaperones; C000717328:PHB protein, human; C000717329:PHB1 protein, S cerevisiae; C000717331:PHB2 protein, human; D000091402:Prohibitins; D011506:Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins