Piecemeal Microautophagy of the Nucleus Requires the Core Macroautophagy Genes

Piecemeal Microautophagy of the Nucleus Requires the Core Macroautophagy Genes
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DOI:
10.1091/mbc.e08-04-0363
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发表时间:
2008-10-01
影响因子:
3.3
通讯作者:
Thumm, M.
Thumm, M.
中科院分区:
生物学3区
文献类型:
--
作者:
Krick, R.;Muehe, Y.;Thumm, M.

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自噬是将细胞质和细胞器转运到溶酶体/空泡腔中进行降解的过程的不同家族。在大自噬期间,货物被包装在与溶酶体/液泡融合的自噬体中。在微自噬过程中,货物直接被溶酶体/空泡膜吞噬。在酿酒酵母中,核的碎片状微自噬(PMN)发生在核-空泡(NV)连接处,并导致核的非必需部分被夹断并释放到空泡中。以往的研究认为,巨自噬ATG基因不是PMN的绝对必需基因。在这里,我们报告使用两个生化检测,有效地抑制中性粒细胞在atg突变细胞:中性粒细胞水泡的产生,但囊泡很少释放到空泡腔。在atg 7,atg 8,和atg 9突变细胞中被捕的PMN结构的电子显微镜检查表明,NV-连接相关的微核通常可以从细胞核中释放之前,其完全封闭的空泡膜。在这方面,PMN类似于过氧化物酶体的微自噬(micropexophagy),其中过氧化物酶体与吞噬空泡相对的一侧被称为“微自噬特异性膜装置”(MIPA)的结构所覆盖。MIPA含有Atg蛋白并促进末端封闭和融合步骤。PMN不需要完整的空泡同型融合基因。我们的结论是一个频谱的ATG基因所需的终端空泡外壳和融合阶段的中性粒细胞。
Autophagy is a diverse family of processes that transport cytoplasm and organelles into the lysosome/vacuole lumen for degradation. During macroautophagy cargo is packaged in autophagosomes that fuse with the lysosome/vacuole. During microautophagy cargo is directly engulfed by the lysosome/vacuole membrane. Piecemeal microautophagy of the nucleus (PMN) occurs in Saccharomyces cerevisiae at nucleus-vacuole (NV) junctions and results in the pinching-off and release into the vacuole of nonessential portions of the nucleus. Previous studies concluded macroautophagy ATG genes are not absolutely required for PMN. Here we report using two biochemical assays that PMN is efficiently inhibited in atg mutant cells: PMN blebs are produced, but vesicles are rarely released into the vacuole lumen. Electron microscopy of arrested PMN structures in atg7, atg8, and atg9 mutant cells suggests that NV-junction-associated micronuclei may normally be released from the nucleus before their complete enclosure by the vacuole membrane. In this regard PMN is similar to the microautophagy of peroxisomes (micropexophagy), where the side of the peroxisome opposite the engulfing vacuole is capped by a structure called the "micropexophagy-specific membrane apparatus" (MIPA). The MIPA contains Atg proteins and facilitates terminal enclosure and fusion steps. PMN does not require the complete vacuole homotypic fusion genes. We conclude that a spectrum of ATG genes is required for the terminal vacuole enclosure and fusion stages of PMN.