title: Mitochondrial alterations induced by the p13II protein of human T-cell leukemia virus type 1. Critical role of arginine residues.
abstract: Human T-cell leukemia virus type 1 encodes a number of "accessory" proteins of unclear function; one of these proteins, p13(II), is targeted to mitochondria and disrupts mitochondrial morphology. The present study was undertaken to unravel the function of p13(II) through (i) determination of its submitochondrial localization and sequences required to alter mitochondrial morphology and (ii) an assessment of the biophysical and biological properties of synthetic peptides spanning residues 9-41 (p13(9-41)), which include the amphipathic mitochondrial-targeting sequence of the protein. p13(9-41) folded into an alpha helix in micellar environments. Fractionation and immunogold labeling indicated that full-length p13(II) accumulates in the inner mitochondrial membrane. p13(9-41) induced energy-dependent swelling of isolated mitochondria by increasing inner membrane permeability to small cations (Na(+), K(+)) and released Ca(2+) from Ca(2+)-preloaded mitochondria. These effects as well as the ability of full-length p13(II) to alter mitochondrial morphology in cells required the presence of four arginines, forming the charged face of the targeting signal. The mitochondrial effects of p13(9-41) were insensitive to cyclosporin A, suggesting that full-length p13(II) might alter mitochondrial permeability through a permeability transition pore-independent mechanism, thus distinguishing it from the mitochondrial proteins Vpr and X of human immunodeficiency virus type 1 and hepatitis B virus, respectively.
authors.affiliation: Department of Oncology and Surgical Sciences, University of Padova, via Gattamelata 64, 35128 Padua, Italy.
authors.forename: Donna M
authors.initials: DM
authors.lastname: D'Agostino
authors.forename: Laura
authors.initials: L
authors.lastname: Ranzato
authors.forename: Giorgio
authors.initials: G
authors.lastname: Arrigoni
authors.forename: Ilaria
authors.initials: I
authors.lastname: Cavallari
authors.forename: Francesca
authors.initials: F
authors.lastname: Belleudi
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Torrisi
authors.forename: Micol
authors.initials: M
authors.lastname: Silic-Benussi
authors.forename: Tiziana
authors.initials: T
authors.lastname: Ferro
authors.forename: Valeria
authors.initials: V
authors.lastname: Petronilli
authors.forename: Oriano
authors.initials: O
authors.lastname: Marin
authors.forename: Luigi
authors.initials: L
authors.lastname: Chieco-Bianchi
authors.forename: Paolo
authors.initials: P
authors.lastname: Bernardi
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Ciminale
mesh_terms: D000595:Amino Acid Sequence; D001120:Arginine; D015368:Human T-lymphotropic virus 1 / Q000737:chemistry*; D006801:Humans; D008564:Membrane Potentials; D008928:Mitochondria / Q000737:chemistry / Q000502:physiology; D008933:Mitochondrial Swelling; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000502:physiology; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012191:Retroviridae Proteins / Q000032:analysis / Q000737:chemistry / Q000502:physiology*; D013329:Structure-Activity Relationship
chemical_list: D010446:Peptide Fragments; D012191:Retroviridae Proteins; C072813:rof protein, Human T-lymphotropic virus 1; D001120:Arginine