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Mitochondrial targeting of the p13II protein coded by the x-II ORF of human T-cell leukemia/lymphotropic virus type I (HTLV-I)

Oncogene volume 18, pages 4505–4514 (1999)Cite this article

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 p13II, an 87-amino acid protein coded by the x-II ORF, is selectively targeted to mitochondria. Mutational analysis revealed that mitochondrial targeting of p13II 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 p13II results in specific alterations of mitochondrial morphology and distribution from a typical string-like, dispersed network to round-shaped clusters, suggesting that p13II 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 p13II-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.

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Acknowledgements

We thank Marta Murgia, Daniela Saggioro and Fabio di Lisa for helpful discussions, Barbara K Felber, George N Pavlakis, Roberto Bisson and Rosario Rizzuto for generously providing plasmids and reagents, and Pierantonio Gallo for preparing the artwork. This study was supported by grants from the Istituto Superiore di Sanita’ (II Progetto AIDS), the Associazione Italiana per la Ricerca sul Cancro (AIRC) and Fondazione Italiana per la Ricerca sul Cancro (FIRC). D M D'Agostino was supported by sequential fellowships from the Istituto Superiore di Sanita'-Progetto AIDS and from the FIRC. L Zotti was supported by a fellowship from the Associazione Italiana per la Lotta contro l'AIDS. The Department of Oncology and Surgical Sciences of the University of Padova participated in the concerted action ‘HTLV European Research Network’ (HERN) of the European Commission Biomed Program.

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Authors and Affiliations

  1. Department of Oncology and Surgical Sciences, University of Padova, Padova, I-35128, Italy

    Vincenzo Ciminale, Lorenza Zotti, Donna M D'Agostino, Tiziana Ferro & Luigi Chieco-Bianchi

  2. Division of Basic Sciences, Basic Research Laboratory, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, Maryland, USA

    Luca Casareto & Genoveffa Franchini

  3. Department of Biomedical Sciences, University of Padova, Padova, I-35121, Italy

    Paolo Bernardi

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  1. Vincenzo Ciminale
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Ciminale, V., Zotti, L., D'Agostino, D. et al. Mitochondrial targeting of the p13II protein coded by the x-II ORF of human T-cell leukemia/lymphotropic virus type I (HTLV-I). Oncogene 18, 4505–4514 (1999). https://doi.org/10.1038/sj.onc.1203047

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