title: Activation-dependent mitochondrial translocation of Foxp3 in human hepatocytes.
abstract: Foxp3 is considered to be the master regulator for the development and function of regulatory T cells (Treg). Recently Foxp3, has been detected in extra lymphoid tissue, and in hepatocytes and has been associated with hepatocellular carcinoma (HCC), although its role has not been defined. Since it is expected that there is a relationship between protein localization, activity and cellular function, the aim of this study was to explore the subcellular localization of Foxp3 in resting and stimulated human hepatocytes. Foxp3 expression was measured by flow cytometry, subcellular fractioning, and immunofluorescence, and this data was used to track the shuttling of Foxp3 in different subcellular compartments in hepatocytes (HepG2 cell line), stimulated by using the PKC activators (PMA), core and preS1/2 antigen from hepatitis B virus (HBV). Our data shows that besides the nuclear location, mitochondrial translocation was detected after stimulation with PMA and at to a lesser extent, with preS1/2. In addition, Foxp3 is localizes at outer mitochondrial membrane. These results suggest a non-canonical role of Foxp3 in the mitochondrial compartment in human hepatocytes, and opens a new field about their role in liver damages during HBV infection.
authors.affiliation: Instituto de Inmunología Clínica, Facultad de Medicina, Universidad de Los Andes, Merida, Venezuela.
authors.forename: Joselyn
authors.initials: J
authors.lastname: Rojas
authors.affiliation: Instituto de Inmunología Clínica, Facultad de Medicina, Universidad de Los Andes, Merida, Venezuela.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Teran-Angel
authors.affiliation: Instituto de Inmunología Clínica, Facultad de Medicina, Universidad de Los Andes, Merida, Venezuela.
authors.forename: Luisa
authors.initials: L
authors.lastname: Barbosa
authors.affiliation: Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: Darrell L
authors.initials: DL
authors.lastname: Peterson
authors.affiliation: Instituto de Inmunología Clínica, Facultad de Medicina, Universidad de Los Andes, Merida, Venezuela; Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address: lberruet@ula.ve.
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Berrueta
authors.affiliation: Instituto de Inmunología Clínica, Facultad de Medicina, Universidad de Los Andes, Merida, Venezuela. Electronic address: sihamsa@ula.ve.
authors.forename: Siham
authors.initials: S
authors.lastname: Salmen
mesh_terms: D000956:Antigens, Viral / Q000378:metabolism; D002451:Cell Compartmentation / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D013347:Subcellular Fractions / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D000956:Antigens, Viral; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D013755:Tetradecanoylphorbol Acetate
keywords: Core; Foxp3; HepG2 cell line; Hepatitis B virus antigens; Human hepatocytes; OMM; Pre 1/2; Subcellular shuttling