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大学・研究所にある論文を検索できる 「Activation of XBP1 but not ATF6α rescues heart failure induced by persistent ER stress in medaka fish」の論文概要。リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

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Activation of XBP1 but not ATF6α rescues heart failure induced by persistent ER stress in medaka fish

Jin, Byungseok Ishikawa, Tokiro Kashima, Makoto Komura, Rei Hirata, Hiromi Okada, Tetsuya Mori, Kazutoshi 京都大学 DOI:10.26508/lsa.202201771

2023.07

概要

The unfolded protein response is triggered in vertebrates by ubiquitously expressed IRE1α/β (although IRE1β is gut-specific in mice), PERK, and ATF6α/β, transmembrane-type sensor proteins in the ER, to cope with ER stress, the accumulation of unfolded and misfolded proteins in the ER. Here, we burdened medaka fish, a vertebrate model organism, with ER stress persistently from fertilization by knocking out the AXER gene encoding an ATP/ADP exchanger in the ER membrane, leading to decreased ATP concentration–mediated impairment of the activity of Hsp70- and Hsp90-type molecular chaperones in the ER lumen. ER stress and apoptosis were evoked from 4 and 6 dpf, respectively, leading to the death of all AXER-KO medaka by 12 dpf because of heart failure (medaka hatch at 7 dpf). Importantly, constitutive activation of IRE1α signaling --but not ATF6α signaling-- rescued this heart failure and allowed AXER-KO medaka to survive 3 d longer, likely because of XBP1-mediated transcriptional induction of ER-associated degradation components. Thus, activation of a specific pathway of the unfolded protein response can cure defects in a particular organ.

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