title: Anion Transport or Nucleotide Binding by Ucp2 Is Indispensable for Ucp2-Mediated Efferocytosis.
abstract: Rapid and efficient engulfment of apoptotic cells is an essential property of phagocytes for removal of the large number of apoptotic cells generated in multicellular organisms. To achieve this, phagocytes need to be able to continuously uptake apoptotic cells. It was recently reported that uncoupling protein 2 (Ucp2) promotes engulfment of apoptotic cells by increasing the phagocytic capacity, thereby allowing cells to continuously ingest apoptotic cells. However, the functions of Ucp2, beyond its possible role in dissipating the mitochondrial membrane potential, that contribute to elevation of the phagocytic capacity have not been determined. Here, we report that the anion transfer or nucleotide binding activity of Ucp2, as well as its dissipation of the mitochondrial membrane potential, is necessary for Ucp2-mediated engulfment of apoptotic cells. To study these properties, we generated Ucp2 mutations that affected three different functions of Ucp2, namely, dissipation of the mitochondrial membrane potential, transfer of anions, and binding of purine nucleotides. Mutations of Ucp2 that affected the proton leak did not enhance the engulfment of apoptotic cells. Although anion transfer and nucleotide binding mutations did not affect the mitochondrial membrane potential, they exerted a dominant-negative effect on Ucp2-mediated engulfment. Furthermore, none of our Ucp2 mutations increased the phagocytic capacity. We conclude that dissipation of the proton gradient by Ucp2 is not the only determinant of the phagocytic capacity and that anion transfer or nucleotide binding by Ucp2 is also essential for Ucp2-mediated engulfment of apoptotic cells.
authors.affiliation: School of Life Sciences and Bio Imaging Research Center, Gwangju Institute of Science and Technology, Gwangju 500-712, Korea.
authors.forename: Suho
authors.initials: S
authors.lastname: Lee
authors.affiliation: School of Life Sciences and Bio Imaging Research Center, Gwangju Institute of Science and Technology, Gwangju 500-712, Korea.|Research Center for Cellular Homeostasis, Ewha Womans University, Seoul 120-750, Korea.
authors.forename: Hyunji
authors.initials: H
authors.lastname: Moon
authors.affiliation: School of Life Sciences and Bio Imaging Research Center, Gwangju Institute of Science and Technology, Gwangju 500-712, Korea.|Research Center for Cellular Homeostasis, Ewha Womans University, Seoul 120-750, Korea.
authors.forename: Gayoung
authors.initials: G
authors.lastname: Kim
authors.affiliation: Department of Biology Education, College of Education, Chosun University, Gwangju 501-759, Korea.
authors.forename: Jeong Hoon
authors.initials: JH
authors.lastname: Cho
authors.forename: Dae-Hee
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Department of Surgery and Pharmacology and Cell Biology, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Lee
authors.initials: L
authors.lastname: Dae-Hee
authors.affiliation: School of Liberal Arts and Sciences, Gwangju Institute of Science and Technology, Gwangju 500-712, Korea.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Ye
authors.affiliation: School of Life Sciences and Bio Imaging Research Center, Gwangju Institute of Science and Technology, Gwangju 500-712, Korea.|Research Center for Cellular Homeostasis, Ewha Womans University, Seoul 120-750, Korea.
authors.forename: Daeho
authors.initials: D
authors.lastname: Park
mesh_terms: D000818:Animals; D017209:Apoptosis; D057809:HEK293 Cells; D006801:Humans; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D017136:Ion Transport; D053078:Membrane Potential, Mitochondrial; D051379:Mice; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D041681:NIH 3T3 Cells; D009711:Nucleotides / Q000378:metabolism*; D010587:Phagocytosis; D011401:Promoter Regions, Genetic; D000071246:Uncoupling Protein 2
chemical_list: D007473:Ion Channels; D024101:Mitochondrial Proteins; D009711:Nucleotides; C000604389:UCP2 protein, human; C000604390:Ucp2 protein, mouse; D000071246:Uncoupling Protein 2
keywords: apoptotic cell; capacity; engulfment; membrane potential; phagocytosis