Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 106 91 Stockholm, Sweden.
Department of Biochemistry and Biophysics, Stockholm University, 106 91 Stockholm, Sweden.
Cells. 2020 May 9;9(5):1184. doi: 10.3390/cells9051184.
In all eukaryotic cells, intracellular organization and spatial separation of incompatible biochemical processes is established by individual cellular subcompartments in form of membrane-bound organelles. Virtually all of these organelles are physically connected via membrane contact sites (MCS), allowing interorganellar communication and a functional integration of cellular processes. These MCS coordinate the exchange of diverse metabolites and serve as hubs for lipid synthesis and trafficking. While this of course indirectly impacts on a plethora of biological functions, including autophagy, accumulating evidence shows that MCS can also directly regulate autophagic processes. Here, we focus on the nexus between interorganellar contacts and autophagy in yeast and mammalian cells, highlighting similarities and differences. We discuss MCS connecting the ER to mitochondria or the plasma membrane, crucial for early steps of both selective and non-selective autophagy, the yeast-specific nuclear-vacuolar tethering system and its role in microautophagy, the emerging function of distinct autophagy-related proteins in organellar tethering as well as novel MCS transiently emanating from the growing phagophore and mature autophagosome.
在所有真核细胞中，通过膜结合细胞器的形式建立了细胞亚区室，以实现生化过程的不相容性的细胞内组织和空间分离。实际上，所有这些细胞器都通过膜接触位点（MCS）物理连接，允许细胞器间的通讯和细胞过程的功能整合。这些 MCS 协调各种代谢物的交换，并作为脂质合成和运输的枢纽。虽然这当然会间接影响包括自噬在内的大量生物学功能，但越来越多的证据表明，MCS 也可以直接调节自噬过程。在这里，我们重点关注酵母和哺乳动物细胞中细胞器间接触与自噬之间的联系，突出相似性和差异性。我们讨论了连接内质网与线粒体或质膜的 MCS，这些 MCS 对选择性和非选择性自噬的早期步骤至关重要，酵母特有的核液连接系统及其在微自噬中的作用，不同的与自噬相关的蛋白质在细胞器连接中的新兴功能，以及从生长的吞噬泡和成熟的自噬体中短暂出现的新的 MCS。
