The p13 protein of human T cell leukemia virus type 1 (HTLV-1) modulates mitochondrial membrane potential and calcium uptake
| Autor: | Paola Aguiari, Roberta Biasiotto, Paolo Pinton, Donna M. D'Agostino, Vincenzo Ciminale, Rosario Rizzuto |
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| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Vesicle-associated membrane protein 8
Recombinant Fusion Proteins Biophysics Retroviridae Proteins Calcium homeostasis HTLV-1 Membrane potential Mitochondria Potassium channel Viroporin Mitochondrion Transfection Biochemistry Models Biological membrane potential calcium homeostasis potassium channel Humans Calcium Signaling Inner mitochondrial membrane Calcium signaling Membrane Potential Mitochondrial Human T-lymphotropic virus 1 Ion Transport biology Cell Biology biology.organism_classification Molecular biology Cell biology Protein Structure Tertiary Mutagenesis Site-Directed Calcium Mutant Proteins HeLa Cells |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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