线粒体在细胞外囊中分泌,当 lysosomal 功能受损时,线粒体会分泌出来
Wenjing Liang1, Shakti Sagar1, Rishith Ravindran1
1Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.
Nature communications
|August 18, 2023
概括
当 lysosomes 失败时,线粒体在细胞外囊泡 (EV) 中分泌,为线粒体清除提供了一条新的途径. 这种囊泡释放在老年心脏和丹农病中被观察到,这表明它在心脏病理生理学中的作用.
科学领域:
- 细胞生物学 细胞生物学
- 心血管生物学 心血管生物学
- 线粒体生物学 线粒体生物学
背景情况:
- 线粒体质量控制对于心脏功能至关重要,通常涉及到受损线粒体的溶酶体降解.
- lysosomal 功能受损可以破坏细胞平衡和能量生产.
研究的目的:
- 在 lysosomal 降解受到损害时,确定线粒体消除的替代机制.
- 为了研究细胞外囊泡 (EVs) 在线粒体清除在 lysosomal 功能障碍条件下的作用.
主要方法:
- 研究了细胞和成年小鼠心中的线粒体分泌物,其 lysosomal 功能受阻.
- 利用Rab7 (一种小GTPase) 的遗传删除来研究其在EV形成和货物分泌中的作用.
- 分析了老老鼠和丹农病患者心脏的EV,以测量线粒体含量.
主要成果:
- 溶酶体抑制触发了大型细胞外囊 (EV) 内完整的线粒体的分泌.
- EV释放是独立于自的,涉及内的途径,Rab7的删除增强了包括线粒体在内的无处不在的载荷的分泌.
- 在老鼠心脏和丹农病患者的心脏中发现了EV中线粒体含量升高的水平.
结论:
- 当 lysosomal 降解被抑制时,通过内体路径通过大型 EVs 来消除线粒体的新途径存在.
- 这种膀型线粒体出口机制与心脏病理生理学有关,特别是在衰老和特定遗传疾病中,如丹恩病.
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