title: The p13 protein of human T cell leukemia virus type 1 (HTLV-1) modulates mitochondrial membrane potential and calcium uptake.
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.
authors.affiliation: Department of Oncology and Surgical Sciences, University of Padova, I-35128 Padova, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Biasiotto
authors.forename: Paola
authors.initials: P
authors.lastname: Aguiari
authors.forename: Rosario
authors.initials: R
authors.lastname: Rizzuto
authors.forename: Paolo
authors.initials: P
authors.lastname: Pinton
authors.forename: Donna M
authors.initials: DM
authors.lastname: D'Agostino
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Ciminale
mesh_terms: D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D006367:HeLa Cells; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D006801:Humans; D017136:Ion Transport; D053078:Membrane Potential, Mitochondrial; D008954:Models, Biological; D016297:Mutagenesis, Site-Directed; D050505:Mutant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012191:Retroviridae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D050505:Mutant Proteins; D011993:Recombinant Fusion Proteins; D012191:Retroviridae Proteins; D002118:Calcium