The p13 protein of human T cell leukemia virus type 1 (HTLV-1) modulates mitochondrial membrane potential and calcium uptake

Roberta Biasiotto, Paola Aguiari, Rosario Rizzuto, Paolo Pinton, Donna M. D'Agostino, Vincenzo Ciminale

Research output: Contribution to journalArticle

Abstract

Human T cell leukemia virus type 1 (HTLV-1) encodes p13, an 87-amino-acid protein that accumulates in the inner mitochondrial membrane. Recent studies performed using synthetic p13 and isolated mitochondria demonstrated that the protein triggers an inward potassium (K+) current and inner membrane depolarization. The present study investigated the effects of p13 on mitochondrial inner membrane potential (δψ) in living cells. Using the potential-dependent probe tetramethyl rhodamine methyl ester (TMRM), we observed that p13 induced dose-dependent mitochondrial depolarization in HeLa cells. This effect was abolished upon mutation of 4 arginines in p13's α-helical domain that were previously shown to be essential for its activity in in vitro assays. As δψ is known to control mitochondrial calcium (Ca2+) uptake, we next analyzed the effect of p13 on Ca2+ homeostasis. Experiments carried out in HeLa cells expressing p13 and organelle-targeted aequorins revealed that the protein specifically reduced mitochondrial Ca2+ uptake. These observations suggest that p13 might control key processes regulated through Ca2+ signaling such as activation and death of T cells, the major targets of HTLV-1 infection.

Original languageEnglish
Pages (from-to)945-951
Number of pages7
JournalBiochimica et Biophysica Acta - Bioenergetics
Volume1797
Issue number6-7
DOIs
Publication statusPublished - Jun 2010

Keywords

  • Calcium homeostasis
  • HTLV-1
  • Membrane potential
  • Mitochondria
  • Potassium channel
  • Viroporin

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology

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