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脂质翻转酶ATP10B使细胞在压力条件下吸收脂质

Rosanne Wouters¹, Igor Beletchi², Chris Van den Haute³

¹Laboratory of Cellular Transport Systems, Department of Cellular and Molecular Medicine, KU Leuven, B-3000 Leuven, Belgium; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA.

Biochimica et biophysica acta. Molecular cell research

|December 12, 2023

概括

脂酶ATP10B在特定的压力条件下促进细胞吸收酸丁胆 (PC),影响帕金森病和痴呆症.

科学领域:

细胞生物学细胞生物学
分子生物学分子生物学
神经科学是一个神经科学.

背景情况:

致病性ATP10B变体与帕金森病和患有勒维体病的痴呆症有关.
ATP10B作为一个晚期的内分/溶酶性脂类飞酶,运输脂胆 (PC) 和葡萄糖胺 (GluCer).
众所周知,其他脂质飞酶也能调节细胞脂质吸收.

研究的目的:

研究ATP10B在细胞脂质吸收中的作用.
为了确定ATP10B是否影响酸丁胆 (PC) 的吸收.

主要方法:

在HeLa细胞中,ATP10B与CDC50A的暂时且稳定的共同表达.
使用光标记的NBD-PC来测量脂质吸收.
在基底条件下和在罗诺治疗 (线粒体复合物I抑制剂) 后评估脂质吸收.
在具有内源ATP10B表达的细胞系中进行ATP10B敲除.

主要成果:

ATP10B/CDC50A共同表达刺激了NBD-PC以一种运输依赖的方式吸收NBD-PC.
与疾病相关的ATP10B变体影响了这种吸收.
在稳定细胞系中,只有在罗诺治疗后才观察到NBD-PC吸收的增加.
ATP10B的淘汰降低了NBD-PC的吸收,这种效应被rotenone压力加剧.

结论:

内分/溶酶性脂质飞酶ATP10B有助于细胞PC吸收.
这种贡献在特定的细胞应激条件下尤其明显,例如线粒体抑制.
这些发现提供了关于ATP10B在脂质运输中的功能及其与神经退行性疾病的潜在相关性的见解.

关键词:

内分/溶解体是内分/溶解体的一种.葡萄糖基胺的含量是多少?脂质运输是指脂质的运输.帕金森病的疾病.酸胆是一种酸.

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