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  1. 教員研究業績
  2. 薬化学研究室
  1. 教員研究業績
  2. 薬化学研究室
  3. 原著論文

A Golgi-targeting fluorescent probe for labile Fe(ii) to reveal an abnormal cellular iron distribution induced by dysfunction of VPS35

https://gifu-pu.repo.nii.ac.jp/records/13453
https://gifu-pu.repo.nii.ac.jp/records/13453
9cc629c1-eddf-4762-a970-8f7a41c7ded8
Item type 会議発表論文 / Conference Paper(1)
公開日 2019-03-04
タイトル
タイトル A Golgi-targeting fluorescent probe for labile Fe(ii) to reveal an abnormal cellular iron distribution induced by dysfunction of VPS35
言語 en
言語
言語 eng
資源タイプ
資源タイプ識別子 http://purl.org/coar/resource_type/c_5794
資源タイプ conference paper
アクセス権
アクセス権 metadata only access
アクセス権URI http://purl.org/coar/access_right/c_14cb
著者 Hirayama, Tasuku

× Hirayama, Tasuku

WEKO 21772

Hirayama, Tasuku

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Inden, Masatoshi

× Inden, Masatoshi

WEKO 21773

Inden, Masatoshi

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Tsuboi, Hitomi

× Tsuboi, Hitomi

WEKO 21774

Tsuboi, Hitomi

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Niwa, Masato

× Niwa, Masato

WEKO 21775

Niwa, Masato

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Uchida, Yasuhiro

× Uchida, Yasuhiro

WEKO 21776

Uchida, Yasuhiro

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Naka, Yuki

× Naka, Yuki

WEKO 21777

Naka, Yuki

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Hozumi, Isao

× Hozumi, Isao

WEKO 21778

Hozumi, Isao

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Nagasawa, Hideko

× Nagasawa, Hideko

WEKO 21779

Nagasawa, Hideko

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抄録
内容記述タイプ Abstract
内容記述 Iron is involved in numerous physiologically essential processes in our body. However, excessive iron is a pathogenic factor in neurodegenerative diseases, causing aberrant oxidative stress. Divalent metal transporter 1 (DMT1) acts as a primary transporter of Fe(II) ions. The intracellular delivery of DMT1 toward the cellular membrane via the trans-Golgi network during the endocytotic process is partially regulated by a retromer-mediated protein-sorting system comprising vacuolar protein-sorting proteins (VPSs). Thus, together with DMT1, the Golgi-apparatus acts as a hub organelle in the delivery system for intracellular Fe(II) ion. Dysfunction of the VPS-relevant protein sorting system can induce the abnormal delivery of DMT1 toward lysosomes concomitantly with Fe(II) ions. To explore this issue, we developed a fluorescent probe, Gol-SiRhoNox for the Golgi-specific detection of Fe(II) ions by integrating our original N-oxide-based Fe(II)-specific chemical switch, a new Golgi-localizable chemical motif, and polarity-sensitive fluorogenic scaffold. Our synchronous imaging study using Gol-SiRhoNox and LysoRhoNox, a previously developed fluorescent probe for lysosomal Fe(II), revealed that the intracellular distribution balance of Fe(II) ions between Golgi apparatus and lysosomes is normally Golgi-dominant, whereas the lysosome-specific elevation of Fe(II) ions was observed in cells with induced dysfunction of VPS35, a member of the retromer complex. Treatment of cells with dysfunctional VPS35 with R55, a molecular chaperone, resulted in the restoration of the subcellular distribution of Fe(II) ions to the Golgi-dominant state. These results indicate that the impairment of the DMT1 traffic machinery affects the subcellular iron homeostasis, promoting Fe(II) leakage at Golgi and lysosomal accumulation of Fe(II) through missorting of DMT1.
書誌情報 en : Chemical Science

巻 10, 号 5, p. 1514-1521, 発行日 2019
ISSN
収録物識別子タイプ ISSN
収録物識別子 2041-6520
DOI
識別子タイプ DOI
関連識別子 10.1039/C8SC04386H
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