Modulation of mitochondrial K+ permeability and reactive oxygen species production by the p13 protein of human T-cell leukemia virus type 1

Micol Silic-Benussi, Enrica Cannizzaro, Andrea Venerando, Ilaria Cavallari, Valeria Petronilli, Nicoletta La Rocca, Oriano Marin, Luigi Chieco-Bianchi, Fabio Di Lisa, Donna M. D'Agostino, Paolo Bernardi, Vincenzo Ciminale

Research output: Contribution to journalArticlepeer-review

Abstract

Human T-cell leukemia virus type-1 (HTLV-1) expresses an 87-amino acid protein named p13 that is targeted to the inner mitochondrial membrane. Previous studies showed that a synthetic peptide spanning an alpha helical domain of p13 alters mitochondrial membrane permeability to cations, resulting in swelling. The present study examined the effects of full-length p13 on isolated, energized mitochondria. Results demonstrated that p13 triggers an inward K+ current that leads to mitochondrial swelling and confers a crescent-like morphology distinct from that caused by opening of the permeability transition pore. p13 also induces depolarization, with a matching increase in respiratory chain activity, and augments production of reactive oxygen species (ROS). These effects require an intact alpha helical domain and strictly depend on the presence of K+ in the assay medium. The effects of p13 on ROS are mimicked by the K+ ionophore valinomycin, while the protonophore FCCP decreases ROS, indicating that depolarization induced by K+ vs. H+ currents has different effects on mitochondrial ROS production, possibly because of their opposite effects on matrix pH (alkalinization and acidification, respectively). The downstream consequences of p13-induced mitochondrial K+ permeability are likely to have an important influence on the redox state and turnover of HTLV-1-infected cells.

Original languageEnglish
Pages (from-to)947-954
Number of pages8
JournalBiochimica et Biophysica Acta - Bioenergetics
Volume1787
Issue number7
DOIs
Publication statusPublished - Jul 2009

Keywords

  • K channel
  • Mitochondria
  • Permeability transition pore
  • Reactive oxygen species

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology

Fingerprint Dive into the research topics of 'Modulation of mitochondrial K+ permeability and reactive oxygen species production by the p13 protein of human T-cell leukemia virus type 1'. Together they form a unique fingerprint.

Cite this