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      KCI등재 SCOPUS SCIE

      The Mitochondrial Fusion-Related Proteins Mfn2 and OPA1 are Transcriptionally Induced during Differentiation of Bone Marrow Progenitors to Immature Dendritic Cells

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      https://www.riss.kr/link?id=A103928123

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      다국어 초록 (Multilingual Abstract)

      The shape and activity of mitochondria are tightly regulated by fusion and fission processes that are essential for maintaining normal cellular function. However, little is known about the involvement of mitochondrial dynamics in the development of the immune system. In this study, we demonstrate that mitochondrial dynamics play a role in the differentiation and migration of immature dendritic cells (imDCs). We show that mitochondrial elongation is induced during GM-CSF-stimulated differentiation of bone marrow progenitors to imDCs accompanied by upregulation of mitochondrial fusion proteins. These processes precede the changes in mitochondrial morphology and connectivity that occur during differentiation. Mfn2 and OPA1, but not Mfn1, are transcriptionally upregulated during differentiation; however, knockdown of Mfn2 and OPA1 does not induce any change in expression of CD11c, CDC80, or CD86. Notably, knockdown of Mfn2 or OPA1 by siRNA in imDCs significantly reduces CCR7 expression and CCL19-mediated migration.
      These results suggest that the mitochondrial fusion- related proteins Mfn2 and OPA1 are upregulated during bone marrow progenitor differentiation and promote the migration of imDCs by regulating the expression of CCR7.
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      The shape and activity of mitochondria are tightly regulated by fusion and fission processes that are essential for maintaining normal cellular function. However, little is known about the involvement of mitochondrial dynamics in the development of th...

      The shape and activity of mitochondria are tightly regulated by fusion and fission processes that are essential for maintaining normal cellular function. However, little is known about the involvement of mitochondrial dynamics in the development of the immune system. In this study, we demonstrate that mitochondrial dynamics play a role in the differentiation and migration of immature dendritic cells (imDCs). We show that mitochondrial elongation is induced during GM-CSF-stimulated differentiation of bone marrow progenitors to imDCs accompanied by upregulation of mitochondrial fusion proteins. These processes precede the changes in mitochondrial morphology and connectivity that occur during differentiation. Mfn2 and OPA1, but not Mfn1, are transcriptionally upregulated during differentiation; however, knockdown of Mfn2 and OPA1 does not induce any change in expression of CD11c, CDC80, or CD86. Notably, knockdown of Mfn2 or OPA1 by siRNA in imDCs significantly reduces CCR7 expression and CCL19-mediated migration.
      These results suggest that the mitochondrial fusion- related proteins Mfn2 and OPA1 are upregulated during bone marrow progenitor differentiation and promote the migration of imDCs by regulating the expression of CCR7.

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      참고문헌 (Reference)

      1 Sallusto, F., "The role of chemokine receptors in primary, effector, and memory immune responses" 18 : 593-620, 2000

      2 Wong, E. D., "The dynamin-related GTPase, Mgm1p, is an intermembrane space protein required for maintenance of fusion competent mitochondria" 151 : 341-352, 2000

      3 Pich, S., "The Charcot-Marie-Tooth type 2A gene product, Mfn2, up-regulates fuel oxidation through expression of OXPHOS system" 14 : 1405-1415, 2005

      4 Del Prete, A., "Role of mitochondria and reactive oxygen species in dendritic cell differentiation and functions" 44 : 1443-1451, 2008

      5 Toki, S., "PGI(2)signaling inhibits antigen uptake and increases migration of immature dendritic cells" 94 : 77-88, 2013

      6 Campello, S., "Orchestration of lymphocyte chemotaxis by mitochondrial dynamics" 203 : 2879-2886, 2006

      7 Wasilewski, M., "Optic atrophy 1-dependent mitochondrial remodeling controls steroidogenesis in trophoblasts" 22 : 1228-1234, 2012

      8 Barbieri, E., "Morphofunctional and biochemical approaches for studying mitochondrial changes during myoblasts differentiation" 2011 : 845379-, 2011

      9 Thundathil, J., "Molecular control of mitochondrial function in preimplantation mouse embryos" 71 : 405-413, 2005

      10 Bach, D., "Mitofusin-2 determines mitochondrial network architecture and mitochondrial metabolism. A novel regulatory mechanism altered in obesity" 278 : 17190-17197, 2003

      1 Sallusto, F., "The role of chemokine receptors in primary, effector, and memory immune responses" 18 : 593-620, 2000

      2 Wong, E. D., "The dynamin-related GTPase, Mgm1p, is an intermembrane space protein required for maintenance of fusion competent mitochondria" 151 : 341-352, 2000

      3 Pich, S., "The Charcot-Marie-Tooth type 2A gene product, Mfn2, up-regulates fuel oxidation through expression of OXPHOS system" 14 : 1405-1415, 2005

      4 Del Prete, A., "Role of mitochondria and reactive oxygen species in dendritic cell differentiation and functions" 44 : 1443-1451, 2008

      5 Toki, S., "PGI(2)signaling inhibits antigen uptake and increases migration of immature dendritic cells" 94 : 77-88, 2013

      6 Campello, S., "Orchestration of lymphocyte chemotaxis by mitochondrial dynamics" 203 : 2879-2886, 2006

      7 Wasilewski, M., "Optic atrophy 1-dependent mitochondrial remodeling controls steroidogenesis in trophoblasts" 22 : 1228-1234, 2012

      8 Barbieri, E., "Morphofunctional and biochemical approaches for studying mitochondrial changes during myoblasts differentiation" 2011 : 845379-, 2011

      9 Thundathil, J., "Molecular control of mitochondrial function in preimplantation mouse embryos" 71 : 405-413, 2005

      10 Bach, D., "Mitofusin-2 determines mitochondrial network architecture and mitochondrial metabolism. A novel regulatory mechanism altered in obesity" 278 : 17190-17197, 2003

      11 Favre, C., "Mitochondrial pyrimidine nucleotide carrier(PNC1)regulates mitochondrial biogenesis and the invasive phenotype of cancer cells" 29 : 3964-3976, 2010

      12 Liesa, M., "Mitochondrial fusion is increased by the nuclear coactivator PGC-1beta" 3 : 3613-, 2008

      13 Zhao, J., "Mitochondrial dynamics regulates migration and invasion of breast cancer cells" 32 : 4814-4824, 2013

      14 Liesa, M., "Mitochondrial dynamics in mammalian health and disease" 89 : 799-845, 2009

      15 Vafai, S. B., "Mitochondrial disorders as windows into an ancient organelle" 491 : 374-383, 2012

      16 Otera, H., "Mff is an essential factor for mitochondrial recruitment of Drp1 during mitochondrial fission in mammalian cells" 191 : 1141-1158, 2010

      17 Detmer, S. A., "Functions and dysfunctions of mitochondrial dynamics" 8 : 870-879, 2007

      18 Dallman, P. R., "Enlargement of mitochondrial compartment in iron and copper deficiency" 35 : 496-505, 1970

      19 Ryu, S. W., "Downregulation of OPA3 is responsible for transforming growth factor-beta-induced mitochondrial elongation and F-actin rearrangement in retinal pigment epithelial ARPE-19 cells" 8 : 63495-, 2013

      20 Banchereau, J., "Dendritic cells and the control of immunity" 392 : 245-252, 1998

      21 Bustos, R. I., "Copper deficiency alters cell bioenergetics and induces mitochondrial fusion through up-regulation of MFN2 and OPA1 in erythropoietic cells" 437 : 426-432, 2013

      22 Santel, A., "Control of mitochondrial morphology by a human mitofusin" 114 : 867-874, 2001

      23 Kraft, C. S., "Control of mitochondrial biogenesis during myogenesis" 290 : 1119-1127, 2006

      24 Zaccagnino, P., "An active mitochondrial biogenesis occurs during dendritic cell differentiation" 44 : 1962-1969, 2012

      25 Caffin, F., "Altered skeletal muscle mitochondrial biogenesis but improved endurance capacity in trained OPA1-deficient mice" 591 : 6017-6037, 2013

      26 Zorzano, A., "Alterations in the mitochondrial regulatory pathways constituted by the nuclear co-factors PGC-1alpha or PGC-1beta and mitofusin 2 in skeletal muscle in type 2 diabetes" 1797 : 1028-1033, 2010

      27 Geissmann, F., "Accumulation of immature Langerhans cells in human lymph nodes draining chronically inflamed skin" 196 : 417-430, 2002

      28 Aihara, T., "A novel potential role for gametogenetin-binding protein 1(GGNBP1)in mitochondrial morphogenesis during spermatogenesis in mice" 80 : 762-770, 2009

      29 Shen, J., "A critical role of mitochondrial phosphatase Ptpmt1 in embryogenesis reveals a mitochondrial metabolic stress-induced differentiation checkpoint in embryonic stem cells" 31 : 4902-4916, 2011

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      학술지 이력
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      2023 평가예정 해외DB학술지평가 신청대상 (해외등재 학술지 평가)
      2020-01-01 평가 등재학술지 유지 (해외등재 학술지 평가) KCI등재
      2012-11-07 학술지명변경 한글명 : 분자와 세포 -> Molecules and Cells KCI등재
      2008-01-01 평가 SCI 등재 (등재유지) KCI등재
      2006-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2004-01-01 평가 등재학술지 유지 (등재유지) KCI등재
      2001-01-01 평가 등재학술지 선정 (등재후보2차) KCI등재
      1998-07-01 평가 등재후보학술지 선정 (신규평가) KCI등재후보
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      기준연도 WOS-KCI 통합IF(2년) KCIF(2년) KCIF(3년)
      2016 2.77 0.19 1.85
      KCIF(4년) KCIF(5년) 중심성지수(3년) 즉시성지수
      1.37 1.11 0.379 0.03
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