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内质网-线粒体界面处的非囊泡脂质运输。

Non-vesicular lipid trafficking at the endoplasmic reticulum-mitochondria interface.

机构信息

Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, University Paris-Sud, Université Paris-Saclay, Gif-sur-Yvette cedex 91198, France

出版信息

Biochem Soc Trans. 2018 Apr 17;46(2):437-452. doi: 10.1042/BST20160185. Epub 2018 Mar 27.

Abstract

Mitochondria are highly dynamic organelles involved in various cellular processes such as energy production, regulation of calcium homeostasis, lipid trafficking, and apoptosis. To fulfill all these functions and preserve their morphology and dynamic behavior, mitochondria need to maintain a defined protein and lipid composition in both their membranes. The maintenance of mitochondrial membrane identity requires a selective and regulated transport of specific lipids from/to the endoplasmic reticulum (ER) and across the mitochondria outer and inner membranes. Since they are not integrated in the classical vesicular trafficking routes, mitochondria exchange lipids with the ER at sites of close apposition called membrane contact sites. Deregulation of such transport activities results in several pathologies including cancer and neurodegenerative disorders. However, we are just starting to understand the function of ER-mitochondria contact sites in lipid transport, what are the proteins involved and how they are regulated. In this review, we summarize recent insights into lipid transport pathways at the ER-mitochondria interface and discuss the implication of recently identified lipid transfer proteins in these processes.

摘要

线粒体是高度动态的细胞器,参与多种细胞过程,如能量产生、钙稳态调节、脂质运输和细胞凋亡。为了发挥所有这些功能并保持其形态和动态行为,线粒体需要在其膜中维持特定的蛋白质和脂质组成。线粒体膜特性的维持需要从内质网(ER)选择性和调节性地运输特定的脂质,并穿过线粒体的外膜和内膜。由于它们不整合到经典的囊泡运输途径中,线粒体在称为膜接触位点的紧密附着部位与 ER 交换脂质。这种运输活动的失调会导致多种疾病,包括癌症和神经退行性疾病。然而,我们才刚刚开始了解 ER-线粒体接触位点在脂质运输中的功能、涉及的蛋白质以及它们是如何被调节的。在这篇综述中,我们总结了 ER-线粒体界面处脂质运输途径的最新研究进展,并讨论了最近鉴定的脂质转移蛋白在这些过程中的作用。

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