Topology-dependent, bifurcated mitochondrial quality control under starvation.
Topology-dependent, bifurcated mitochondrial quality control under starvation.
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饥饿条件下拓扑依赖的分叉线粒体质量控制
DOI：
10.1080/15548627.2019.1634944
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发表时间：
2019
期刊：
影响因子：
13.3
通讯作者：
Xingguo Liu
中科院分区：
文献类型：
--
作者：
Yanshuang Zhou;Qi Long;Hao Wu;Wei Li;Juntao Qi;Yi Wu;Ge Xiang;Haite Tang;Liang Yang;Keshi Chen;Linpeng Li;Feixiang Bao;Heying Li;Yaofeng Wang;Min Li;Xingguo Liu
通过自噬选择性消除线粒体是多种生理过程的关键策略，包括发育、细胞命运决定和应激反应。尽管已经确定了几种机制负责线粒体的选择性降解，如PINK 1-PRKN/PARKIN-和受体依赖性途径，但这些机制的各个方面，特别是线粒体选择过程的基本原理仍然不清楚。在这里，我们提出了一种新的选择策略，其中线粒体的选择性消除依赖于细胞器拓扑结构。我们发现，血清饥饿下的线粒体群体进行不同的拓扑结构的转换，无论是肿胀或形成甜甜圈形状。Swedish线粒体与线粒体膜电位耗散和PRKN募集相关，这促进了它们的选择性消除，而甜甜圈拓扑结构维持线粒体膜电位并帮助线粒体抵抗自噬。机制研究表明，即使在PRKN募集后，甜甜圈也通过阻止自噬体受体CALCOCO 2/NDP 52和OPTN的募集来抵抗自噬，即使在去极化后也是如此。我们的研究结果表明，拓扑依赖性，分叉的线粒体循环饥饿下，即肿胀的线粒体进行自噬去除，而甜甜圈线粒体进行裂变和融合周期的重新整合。这项研究揭示了一种新的形态选择控制线粒体的质量和数量在饥饿。
Selective elimination of mitochondria by autophagy is a critical strategy for a variety of physiological processes, including development, cell-fate determination and stress response. Although several mechanisms have been identified as responsible for selective degradation of mitochondria, such as the PINK1-PRKN/PARKIN- and receptor-dependent pathways, aspects of the mechanisms and particularly the principles underlying the selection process of mitochondria remain obscure. Here, we addressed a new selection strategy in which the selective elimination of mitochondria is dependent on organellar topology. We found that populations of mitochondria undergo different topological transformations under serum starvation, either swelling or forming donut shapes. Swollen mitochondria are associated with mitochondrial membrane potential dissipation and PRKN recruitment, which promote their selective elimination, while the donut topology maintains mitochondrial membrane potential and helps mitochondria resist autophagy. Mechanistic studies show that donuts resist autophagy even after depolarization through preventing recruitment of autophagosome receptors CALCOCO2/NDP52 and OPTN even after PRKN recruitment. Our results demonstrate topology-dependent, bifurcated mitochondrial recycling under starvation, that is swollen mitochondria undergo removal by autophagy, while donut mitochondria undergo fission and fusion cycles for reintegration. This study reveals a novel morphological selection for control of mitochondrial quality and quantity under starvation.