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Atg43 将隔离膜与线粒体连接起来,以促进裂殖酵母在饥饿诱导下的线粒体自噬。

Atg43 tethers isolation membranes to mitochondria to promote starvation-induced mitophagy in fission yeast.

机构信息

Department of Cellular Physiology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

Omics Unit, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

出版信息

Elife. 2020 Nov 3;9:e61245. doi: 10.7554/eLife.61245.

Abstract

Degradation of mitochondria through mitophagy contributes to the maintenance of mitochondrial function. In this study, we identified that Atg43, a mitochondrial outer membrane protein, serves as a mitophagy receptor in the model organism to promote the selective degradation of mitochondria. Atg43 contains an Atg8-family-interacting motif essential for mitophagy. Forced recruitment of Atg8 to mitochondria restores mitophagy in Atg43-deficient cells, suggesting that Atg43 tethers expanding isolation membranes to mitochondria. We found that the mitochondrial import factors, including the Mim1-Mim2 complex and Tom70, are crucial for mitophagy. Artificial mitochondrial loading of Atg43 bypasses the requirement of the import factors, suggesting that they contribute to mitophagy through Atg43. Atg43 not only maintains growth ability during starvation but also facilitates vegetative growth through its mitophagy-independent function. Thus, Atg43 is a useful model to study the mechanism and physiological roles, as well as the origin and evolution, of mitophagy in eukaryotes.

摘要

线粒体通过自噬作用降解有助于维持线粒体功能。在这项研究中,我们鉴定出线粒体外膜蛋白 Atg43 在模式生物中作为自噬受体,促进线粒体的选择性降解。Atg43 含有一个 Atg8 家族相互作用基序,对于自噬是必需的。Atg8 被强制招募到线粒体中,恢复了 Atg43 缺陷细胞中的自噬作用,这表明 Atg43 将扩张的隔离膜系在到线粒体上。我们发现,包括 Mim1-Mim2 复合物和 Tom70 在内的线粒体导入因子对于自噬是至关重要的。人工线粒体加载 Atg43 绕过了导入因子的要求,这表明它们通过 Atg43 促进自噬。Atg43 不仅在饥饿期间保持生长能力,而且通过其非自噬依赖性功能促进营养生长。因此,Atg43 是研究真核生物自噬的机制和生理作用以及起源和进化的有用模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1fd5/7609059/4e75e7d7dbaf/elife-61245-fig1.jpg

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