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ID 116483
著者
Kojima, Waka Tokyo Metropolitan Institute of Medical Science|The University of Tokyo
Yamano, Koji Tokyo Metropolitan Institute of Medical Science
Imai, Kenichiro National Institute of Advanced Industrial Science and Technology
Kikuchi, Reika Tokyo Metropolitan Institute of Medical Science
Tanaka, Keiji Tokyo Metropolitan Institute of Medical Science
Matsuda, Noriyuki Tokyo Metropolitan Institute of Medical Science
キーワード
Mitophagy
phagophore
parkin
pink1
starvation
wd40
資料タイプ
学術雑誌論文
抄録
Macroautophagy/autophagy is an intracellular degradation process that delivers cytosolic materials and/or damaged organelles to lysosomes. De novo synthesis of the autophagosome membrane occurs within a phosphatidylinositol-3-phosphate-rich region of the endoplasmic reticulum, and subsequent expansion is critical for cargo encapsulation. This process is complex, especially in mammals, with many regulatory factors. In this study, by utilizing PRKN (parkin RBR E3 ubiquitin protein ligase)-mediated mitochondria autophagy (mitophagy)-inducing conditions in conjunction with chemical crosslinking and mass spectrometry, we identified human BCAS3 (BCAS3 microtubule associated cell migration factor) and C16orf70 (chromosome 16 open reading frame 70) as novel proteins that associate with the autophagosome formation site during both non-selective and selective autophagy. We demonstrate that BCAS3 and C16orf70 form a complex and that their association with the phagophore assembly site requires both proteins. In silico structural modeling, mutational analyses in cells and in vitro phosphoinositide-binding assays indicate that the WD40 repeat domain in human BCAS3 directly binds phosphatidylinositol-3-phosphate. Furthermore, overexpression of the BCAS3-C16orf70 complex affects the recruitment of several core autophagy proteins to the phagophore assembly site. This study demonstrates regulatory roles for human BCAS3 and C16orf70 in autophagic activity.
掲載誌名
Autophagy
ISSN
15548627
15548635
cat書誌ID
AA12157457
AA12814026
出版者
Taylor & Francis
17
8
開始ページ
2011
終了ページ
2036
発行日
2021-01-26
権利情報
This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.
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出版社版DOI
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フルテキストファイル
言語
eng
著者版フラグ
出版社版
部局
先端酵素学研究所