CBS/H2S的Miro2硫酸化作用通过调节线粒体动力学促进人类滋养细胞的侵袭和迁移。

IF 8.1 1区 生物学 Q1 CELL BIOLOGY
Hao Feng, Zongxin Sun, Baoshi Han, Huitang Xia, Lumei Chen, Chunlei Tian, Suhua Yan, Yugen Shi, Jie Yin, Wengang Song, Peipei Gong, Shuanglian Wang, Yan Li
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引用次数: 0

摘要

细胞母细胞(CTB)迁移和侵入母体子宫肌层不足会导致妊娠相关并发症,如宫内生长受限(IUGR)和先兆子痫(PE)。我们以前曾发现硫化氢(H2S)能增强 CTB 的迁移,但却不知道其机制和病理生理意义。通过研究人体样本和细胞系,我们发现 PE 患者血浆中的 H2S 水平较低;H2S 合成酶胱硫醚 β-合成酶(CBS)在 PE 非绒毛膜浸润性滋养细胞中减少。GYY4137(H2S 供体,1 µM)可促进 CBS/H2S 转位至线粒体,保护线粒体功能,增强细胞侵袭和迁移。敲除 CBS 会阻碍上述功能的发挥,而 GYY4137 则能挽救这些功能,这表明 CBS/H2S 信号具有重要作用。线粒体动力学紊乱抑制了细胞的侵袭和迁移。线粒体 Rho GTPase 2(Miro2C185/C504)的 185 和 504 半胱氨酸被 H2S 高度硫水化。敲除Miro2或将Miro2C185/C504双突变为丝氨酸会使线粒体破碎,并抑制细胞的侵袭和迁移,而H2S则无法挽救。本研究表明,人类细胞母细胞接受低剂量 H2S 的调控;CBS/H2S 通过 Miro2C185/C504 的硫水化作用维持线粒体的功能,从而增强细胞母细胞的移动性。这些发现为细胞母细胞功能建立了新的调控途径,并为 IUGR 和 PE 提供了新的靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Miro2 sulfhydration by CBS/H2S promotes human trophoblast invasion and migration via regulating mitochondria dynamics.

Insufficient cytotrophoblast (CTB) migration and invasion into the maternal myometrium leads to pregnancy related complications like Intra-uterus Growth Restriction (IUGR), and pre-eclampsia (PE). We previously found that hydrogen sulfide (H2S) enhanced CTB migration without knowing the mechanism(s) and the pathophysiological significance. By studying human samples and cell line, we found that H2S levels were lower in PE patients' plasma; H2S synthetic enzyme cystathionine β-synthetase (CBS) was reduced in PE extravillious invasive trophoblasts. GYY4137 (H2S donor, 1 µM) promoted CBS/H2S translocation onto mitochondria, preserved mitochondria functions, enhanced cell invasion and migration. CBS knockdown hindered the above functions which were rescued by GYY4137, indicating the vital roles of CBS/H2S signal. Disturbance of mitochondria dynamics inhibited cell invasion and migration. The 185 and 504 cysteines of Mitochondrial Rho GTPase 2 (Miro2C185/C504) were highly sulfhydrated by H2S. Knockdown Miro2 or double mutation of Miro2C185/C504 to serine fragmented mitochondria, and inhibited cell invasion and migration which can't be rescued by H2S. The present study showed that human cytotrophoblast receives low dose H2S regulation; CBS/H2S sustained mitochondria functions via Miro2C185/C504 sulfhydration to enhance cytotrophoblast mobility. These findings established a new regulatory pathway for cytotrophoblast functions, and provided new targets for IUGR and PE.

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来源期刊
Cell Death & Disease
Cell Death & Disease CELL BIOLOGY-
CiteScore
15.10
自引率
2.20%
发文量
935
审稿时长
2 months
期刊介绍: Brought to readers by the editorial team of Cell Death & Differentiation, Cell Death & Disease is an online peer-reviewed journal specializing in translational cell death research. It covers a wide range of topics in experimental and internal medicine, including cancer, immunity, neuroscience, and now cancer metabolism. Cell Death & Disease seeks to encompass the breadth of translational implications of cell death, and topics of particular concentration will include, but are not limited to, the following: Experimental medicine Cancer Immunity Internal medicine Neuroscience Cancer metabolism
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