Mitochondrial alterations induced by the p13 II protein of human T-cell leukemia virus type 1: Critical role of arginine residues

Donna M. D'Agostino, Laura Ranzato, Giorgio Arrigoni, Ilaria Cavallari, Francesca Belleudi, Maria Rosaria Torrisi, Micol Silic-Benussi, Tiziana Ferro, Valeria Petronilli, Oriano Marin, Luigi Chieco-Bianchi, Paolo Bernardi, Vincenzo Ciminale

Research output: Contribution to journalArticlepeer-review

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 α 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.

Original languageEnglish
Pages (from-to)34424-34433
Number of pages10
JournalJournal of Biological Chemistry
Volume277
Issue number37
DOIs
Publication statusPublished - Sep 13 2002

ASJC Scopus subject areas

  • Biochemistry

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