1. The p13 protein of human T cell leukemia virus type 1 (HTLV-1) modulates mitochondrial membrane potential and calcium uptake.
- Author
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Biasiotto R, Aguiari P, Rizzuto R, Pinton P, D'Agostino DM, and Ciminale V
- Subjects
- Calcium Signaling, HeLa Cells, Human T-lymphotropic virus 1 genetics, Human T-lymphotropic virus 1 pathogenicity, Humans, Ion Transport, Models, Biological, Mutagenesis, Site-Directed, Mutant Proteins chemistry, Mutant Proteins genetics, Mutant Proteins metabolism, Protein Structure, Tertiary, Recombinant Fusion Proteins chemistry, Recombinant Fusion Proteins genetics, Recombinant Fusion Proteins metabolism, Retroviridae Proteins chemistry, Retroviridae Proteins genetics, Transfection, Calcium metabolism, Human T-lymphotropic virus 1 metabolism, Membrane Potential, Mitochondrial, Retroviridae Proteins metabolism
- 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 (Deltapsi) 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 alpha-helical domain that were previously shown to be essential for its activity in in vitro assays. As Deltapsi 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., (Copyright © 2010 Elsevier B.V. All rights reserved.)
- Published
- 2010
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