Tsukamoto Satoshi, Kuma Akiko, Murakami Mirei, Kishi Chieko, Yamamoto Akitsugu, Mizushima Noboru
Department of Physiology and Cell Biology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Science. 2008 Jul 4;321(5885):117-20. doi: 10.1126/science.1154822.
After fertilization, maternal proteins in oocytes are degraded and new proteins encoded by the zygotic genome are synthesized. We found that autophagy, a process for the degradation of cytoplasmic constituents in the lysosome, plays a critical role during this period. Autophagy was triggered by fertilization and up-regulated in early mouse embryos. Autophagy-defective oocytes derived from oocyte-specific Atg5 (autophagy-related 5) knockout mice failed to develop beyond the four- and eight-cell stages if they were fertilized by Atg5-null sperm, but could develop if they were fertilized by wild-type sperm. Protein synthesis rates were reduced in the autophagy-null embryos. Thus, autophagic degradation within early embryos is essential for preimplantation development in mammals.
受精后,卵母细胞中的母体蛋白质会被降解,由合子基因组编码的新蛋白质会被合成。我们发现,自噬(一种在溶酶体中降解细胞质成分的过程)在此期间发挥着关键作用。自噬由受精触发,并在早期小鼠胚胎中上调。来自卵母细胞特异性Atg5(自噬相关5)基因敲除小鼠的自噬缺陷型卵母细胞,如果与Atg5基因缺失的精子受精,将无法发育到四细胞和八细胞阶段以上,但如果与野生型精子受精则可以发育。自噬缺失的胚胎中蛋白质合成速率降低。因此,早期胚胎内的自噬降解对于哺乳动物的植入前发育至关重要。