Receptor-mediated selective autophagy degrades the endoplasmic reticulum and the nucleus
Receptor-mediated selective autophagy degrades the endoplasmic reticulum and the nucleus
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DOI：
10.1038/nature14506
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发表时间：
2015-06-18
期刊：
影响因子：
64.8
通讯作者：
Nakatogawa, Hitoshi
中科院分区：
文献类型：
--
作者：
Mochida, Keisuke;Oikawa, Yu;Nakatogawa, Hitoshi
巨噬（Macroautophagy，以下简称自噬）降解多种细胞内成分，调节多种细胞功能，并与多种人类疾病密切相关（1,2）。在选择性自噬中，受体蛋白识别降解目标，并通过称为自噬体的双膜囊泡将其隔离，并将其转运到溶酶体或液泡中(3)。尽管最近的研究表明，选择性自噬参与了一些细胞器的质量/数量控制，包括线粒体和过氧化物酶体(4)，但它对细胞器稳态的贡献程度仍不清楚。本文描述了酵母内质网（ER）和细胞核的选择性自噬。我们发现了两个新的蛋白，Atg39和Atg40，作为这些途径的特异性受体。Atg39定位于核周内质网（或核膜）并诱导部分核的自噬隔离。Atg40富集于皮质和细胞质内质网，并将这些内质网亚域装载到自噬体中。氮剥夺条件下，核周ER/细胞核的atg39依赖性自噬是细胞存活所必需的。Atg40可能是FAM134B的功能对应物，FAM134B是哺乳动物内质网的自噬受体，与感觉神经病变有关(5)。我们的研究结果为其他生物中“er吞噬”和“核吞噬”的病理生理作用和机制提供了基本的见解。
Macroautophagy (hereafter referred to as autophagy) degrades various intracellular constituents to regulate a wide range of cellular functions, and is also closely linked to several human diseases(1,2). In selective autophagy, receptor proteins recognize degradation targets and direct their sequestration by double-membrane vesicles called autophagosomes, which transport them into lysosomes or vacuoles(3). Although recent studies have shown that selective autophagy is involved in quality/quantity control of some organelles, including mitochondria and peroxisomes(4), it remains unclear how extensively it contributes to cellular organelle homeostasis. Here we describe selective autophagy of the endoplasmic reticulum (ER) and nucleus in the yeast Saccharomyces cerevisiae. We identify two novel proteins, Atg39 and Atg40, as receptors specific to these pathways. Atg39 localizes to the perinuclear ER (or the nuclear envelope) and induces autophagic sequestration of part of the nucleus. Atg40 is enriched in the cortical and cytoplasmic ER, and loads these ER subdomains into autophagosomes. Atg39-dependent autophagy of the perinuclear ER/nucleus is required for cell survival under nitrogen-deprivation conditions. Atg40 is probably the functional counterpart of FAM134B, an autophagy receptor for the ER in mammals that has been implicated in sensory neuropathy(5). Our results provide fundamental insight into the pathophysiological roles and mechanisms of 'ER-phagy' and 'nucleophagy' in other organisms.