Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Anion Transport or Nucleotide Binding by Ucp2 Is Indispensable for Ucp2-Mediated Efferocytosis

  • Lee, Suho (School of Life Sciences and Bio Imaging Research Center, Gwangju Institute of Science and Technology) ;
  • Moon, Hyunji (School of Life Sciences and Bio Imaging Research Center, Gwangju Institute of Science and Technology) ;
  • Kim, Gayoung (School of Life Sciences and Bio Imaging Research Center, Gwangju Institute of Science and Technology) ;
  • Cho, Jeong Hoon (Department of Biology Education, College of Education, Chosun University) ;
  • Lee, Dae-Hee (Department of Surgery and Pharmacology and Cell Biology, School of Medicine, University of Pittsburgh) ;
  • Ye, Michael B. (School of Liberal Arts and Sciences, Gwangju Institute of Science and Technology) ;
  • Park, Daeho (School of Life Sciences and Bio Imaging Research Center, Gwangju Institute of Science and Technology)
  • Received : 2015.03.30
  • Accepted : 2015.04.16
  • Published : 2015.07.31
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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.

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References

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