The role of autophagy during the early neonatal starvation period
The role of autophagy during the early neonatal starvation period
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DOI：
10.1038/nature03029
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发表时间：
2004-12-23
期刊：
影响因子：
64.8
通讯作者：
Mizushima, N
中科院分区：
文献类型：
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作者：
Kuma, A;Hatano, M;Mizushima, N
出生时，经胎盘的营养供应突然中断，新生儿面临严重饥饿，直至通过乳汁营养得以恢复（1）。在此，我们表明新生儿通过诱导自噬来适应这种不利情况。自噬是溶酶体内细胞质成分降解的主要方式（2 - 4）。小鼠胚胎发育期间自噬水平较低；然而，出生后自噬在各种组织中立即上调，并在3 - 12小时内维持在较高水平，1 - 2天内恢复到基础水平。缺乏Atg5（自噬体形成所必需的）的小鼠出生时看似几乎正常，但在出生后1天内死亡。饥饿的Atg5缺陷型新生儿的存活时间（约12小时）比野生型小鼠（约21小时）短得多，但通过强制喂奶可延长存活时间。Atg5缺陷型新生儿血浆和组织中的氨基酸浓度降低，并表现出能量耗尽的迹象。这些结果表明，通过对“自身”蛋白质进行自噬降解产生氨基酸，从而维持能量稳态，对新生儿饥饿期间的生存至关重要。
At birth the trans-placental nutrient supply is suddenly interrupted, and neonates face severe starvation until supply can be restored through milk nutrients(1). Here, we show that neonates adapt to this adverse circumstance by inducing autophagy. Autophagy is the primary means for the degradation of cytoplasmic constituents within lysosomes(2-4). The level of autophagy in mice remains low during embryogenesis; however, autophagy is immediately upregulated in various tissues after birth and is maintained at high levels for 3 - 12 h before returning to basal levels within 1 - 2 days. Mice deficient for Atg5, which is essential for autophagosome formation, appear almost normal at birth but die within 1 day of delivery. The survival time of starved Atg5-deficient neonates (similar to 12 h) is much shorter than that of wild-type mice (similar to21 h) but can be prolonged by forced milk feeding. Atg5-deficient neonates exhibit reduced amino acid concentrations in plasma and tissues, and display signs of energy depletion. These results suggest that the production of amino acids by autophagic degradation of 'self' proteins, which allows for the maintenance of energy homeostasis, is important for survival during neonatal starvation.