title: Membrane protein degradation by AAA proteases in mitochondria: extraction of substrates from either membrane surface.
abstract: Two AAA proteases, each with its catalytic site at the opposite membrane surface, mediate the ATP-dependent degradation of mitochondrial inner membrane proteins. We demonstrate here that a model substrate polypeptide containing hydrophilic domains at both sides of the membrane can be completely degraded by either of the AAA proteases, if solvent-exposed domains are in an unfolded state. A short protein tail protruding from the membrane surface is sufficient to allow the proteolytic attack of an AAA protease that facilitates domain unfolding at the opposite side. Our results provide a rationale for the membrane arrangement of AAA proteases in mitochondria and demonstrate that degradation of membrane proteins by AAA proteases involves an active extraction of transmembrane segments and transport of solvent-exposed domains across the membrane.
authors.affiliation: Adolf-Butenandt-Institut für Physiologische Chemie, Universität München, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Leonhard
authors.forename: B
authors.initials: B
authors.lastname: Guiard
authors.forename: G
authors.initials: G
authors.lastname: Pellecchia
authors.forename: A
authors.initials: A
authors.lastname: Tzagoloff
authors.forename: W
authors.initials: W
authors.lastname: Neupert
authors.forename: T
authors.initials: T
authors.lastname: Langer
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism*; D005656:Fungal Proteins / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000378:metabolism*; D008928:Mitochondria / Q000201:enzymology*; D011489:Protein Denaturation; D017510:Protein Folding; D013379:Substrate Specificity; D015003:Yeasts
chemical_list: D005656:Fungal Proteins; D008565:Membrane Proteins; D008666:Metalloendopeptidases; C114583:m-AAA proteases; D000251:Adenosine Triphosphatases