title: Towards the control of intracellular protein turnover: mitochondrial Lon protease inhibitors versus proteasome inhibitors.
abstract: Cellular protein homeostasis results from the combination of protein biogenesis processes and protein quality control mechanisms, which contribute to the functional state of cells under normal and stress conditions. Proteolysis constitutes the final step by which short-lived, misfolded and damaged intracellular proteins are eliminated. Protein turnover and oxidatively modified protein degradation are mainly achieved by the proteasome in the cytosol and nucleus of eukaryotic cells while several ATP-dependent proteases including the matrix protease Lon take part in the mitochondrial protein degradation. Moreover, Lon protease seems to play a major role in the elimination of oxidatively modified proteins in the mitochondrial matrix. Specific inhibitors are commonly used to assess cellular functions of proteolytic systems as well as to identify their protein substrates. Here, we present and discuss known proteasome and Lon protease inhibitors. To date, very few inhibitors of Lon have been described and no specific inhibitors of this protease are available. The current knowledge on both catalytic mechanisms and inhibitors of these two proteases is first described and attempts to define specific non-peptidic inhibitors of the human Lon protease are presented.
authors.affiliation: Laboratoire de Biologie et Biochimie Cellulaire du Vieillissement, EA 3106 / IFR 117, Université Paris 7-Denis Diderot, 2 place Jussieu, Tour 33-23, 1(er) étage, CC 7128, 75251 Paris cedex 05, France.
authors.forename: Aurélien
authors.initials: A
authors.lastname: Bayot
authors.forename: Nicolas
authors.initials: N
authors.lastname: Basse
authors.forename: Irene
authors.initials: I
authors.lastname: Lee
authors.forename: Monique
authors.initials: M
authors.lastname: Gareil
authors.forename: Bernard
authors.initials: B
authors.lastname: Pirotte
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Bulteau
authors.forename: Bertrand
authors.initials: B
authors.lastname: Friguet
authors.forename: Michèle
authors.initials: M
authors.lastname: Reboud-Ravaux
mesh_terms: D002384:Catalysis; D006801:Humans; D008928:Mitochondria / Q000201:enzymology*; D024101:Mitochondrial Proteins / Q000378:metabolism; D011480:Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D049070:Protease La / Q000737:chemistry* / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry* / Q000378:metabolism
chemical_list: D024101:Mitochondrial Proteins; D011480:Protease Inhibitors; D049070:Protease La; D046988:Proteasome Endopeptidase Complex