Mitochondrial targeting of the p13(II) protein coded by the x-II ORF of human T-cell leukemia/lymphotropic virus type I (HTLV-I)

Vincenzo Ciminale, Lorenza Zotti, Donna M. D'Agostino, Tiziana Ferro, Luca Casareto, Genoveffa Franchini, Paolo Bernardi, Luigi Chieco-Bianchi

Research output: Contribution to journalArticle

Abstract

The X region of the HTLV-I genome contains four major open reading frames (ORFs), two of which, termed x-I and x-II, are of still undefined biological significance. By indirect immunofluorescence and dual labeling with marker proteins, we demonstrate that p13(II), an 87-amino acid protein coded by the x-II ORF, is selectively targeted to mitochondria. Mutational analysis revealed that mitochondrial targeting of p13(II) is directed by an atypical 10-amino acid signal sequence that is not cleaved upon import and is able to target the Green Fluorescent Protein to mitochondria. Expression of p13(II) results in specific alterations of mitochondrial morphology and distribution from a typical string-like, dispersed network to round-shaped clusters, suggesting that p13(II) might interfere with processes relying on an intact mitochondrial architecture. Functional studies of mitochondria with the cationic fluorochrome tetramethylrhodamine revealed that a subpopulation of the cells with p13(II)-positive mitochondria show a disruption in the mitochondrial inner membrane potential (Δψ), an early event observed in cells committed to apoptosis. Taken together, these results suggest novel virus-cell interactions that might be important in HTLV-I replication and/or pathogenicity.

Original languageEnglish
Pages (from-to)4505-4514
Number of pages10
JournalOncogene
Volume18
Issue number31
DOIs
Publication statusPublished - Aug 5 1999

Keywords

  • Δψ
  • HTLV
  • Mitochondria
  • p13(II)
  • X region

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Biology

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    Ciminale, V., Zotti, L., D'Agostino, D. M., Ferro, T., Casareto, L., Franchini, G., Bernardi, P., & Chieco-Bianchi, L. (1999). Mitochondrial targeting of the p13(II) protein coded by the x-II ORF of human T-cell leukemia/lymphotropic virus type I (HTLV-I). Oncogene, 18(31), 4505-4514. https://doi.org/10.1038/sj.onc.1203047