title: Dissection of the carboxyl-terminal domain of the proteasomal subunit Rpn11 in maintenance of mitochondrial structure and function.
abstract: We have previously demonstrated that the C-terminal part of Rpn11, a deubiquitinating enzyme in the lid of the proteasome, is essential for maintaining a correct cell cycle and normal mitochondrial morphology and function. The two roles are apparently unlinked as the mitochondrial role is mapped to the Carboxy-terminus, whereas the catalytic deubiquitinating activity is found within the N-terminal region. The mitochondrial defects are observed in rpn11-m1 (originally termed mpr1-1), a mutation that generates Rpn11 lacking the last 31 amino acids. No mitochondrial phenotypes are recorded for mutations in the MPN+/JAMM motif. In the present study, we investigated the participation of the last 31 amino acids of the Rpn11 protein by analysis of intragenic revertants and site-specific mutants. We identified a putative alpha-helix necessary for the maintenance of a correct cell cycle and determined that a very short region at the C-terminus of Rpn11 is essential for the maintenance of tubular mitochondrial morphology. Furthermore, we show that expression of the C-terminal part of Rpn11 is able to complement in trans all of the rpn11-m1 mitochondrial phenotypes. Finally, we investigate the mechanisms by which Rpn11 controls the mitochondrial shape and show that Rpn11 may regulate the mitochondrial fission and tubulation processes.
authors.affiliation: Pasteur Institute-Cenci Bolognetti Foundation, Department of Cell and Developmental Biology, University of Rome La Sapienza, 00185 Rome, Italy. teresa.rinaldi@uniroma1.it
authors.forename: Teresa
authors.initials: T
authors.lastname: Rinaldi
authors.forename: Line
authors.initials: L
authors.lastname: Hofmann
authors.forename: Alessia
authors.initials: A
authors.lastname: Gambadoro
authors.forename: Raynald
authors.initials: R
authors.lastname: Cossard
authors.forename: Nurit
authors.initials: N
authors.lastname: Livnat-Levanon
authors.forename: Michael H
authors.initials: MH
authors.lastname: Glickman
authors.forename: Laura
authors.initials: L
authors.lastname: Frontali
authors.forename: Agnès
authors.initials: A
authors.lastname: Delahodde
mesh_terms: D000595:Amino Acid Sequence; D010450:Endopeptidases / Q000737:chemistry* / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010101:Oxygen Consumption; D010641:Phenotype; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry* / Q000378:metabolism*; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013489:Suppression, Genetic
chemical_list: D021122:Protein Subunits; C115451:RPN11 protein, S cerevisiae; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D049452:Green Fluorescent Proteins; D010450:Endopeptidases; D046988:Proteasome Endopeptidase Complex