The role of autophagy during the early neonatal starvation period (original) (raw)

Nature volume 432, pages 1032–1036 (2004)Cite this article

Abstract

At birth the trans-placental nutrient supply is suddenly interrupted, and neonates face severe starvation until supply can be restored through milk nutrients1. 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 lysosomes2,3,4. 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 (∼ 12 h) is much shorter than that of wild-type mice (∼ 21 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.

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Acknowledgements

We thank M. Miwa and H. Satake for technical assistance. We also thank S. Sugano for donation of the pEF321-T plasmid; K. Ono and K. Tanaka for histological examination of the brain; M. Tamagawa for instruction in electrocardiogram recording; and S. Nishio, N. Tsunekawa and M. Terai for discussions. Amino acid measurements were carried out with the aid of the Center for Analytical Instruments at the National Institute for Basic Biology. This work was supported in part by Grants-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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Authors and Affiliations

  1. Time's Arrow and Biosignaling, PRESTO, Japan Science and Technology Agency, 332-0012, Kawaguchi, Japan
    Akiko Kuma & Noboru Mizushima
  2. Department of Developmental Genetics (H2), Chiba University, 260-8670, Chiba, Japan
    Akiko Kuma, Masahiko Hatano & Takeshi Tokuhisa
  3. Department of Pharmacology (F2), Chiba University Graduate School of Medicine, Chiba University, 260-8670, Chiba, Japan
    Haruaki Nakaya
  4. Biomedical Research Center, Chiba University, 260-8670, Chiba, Japan
    Masahiko Hatano
  5. Department of Cell Biology, National Institute for Basic Biology, he Graduate University for Advanced Studies, 444-8585, Okazaki, Japan
    Akiko Kuma, Makoto Matsui, Yoshinori Ohsumi & Noboru Mizushima
  6. Department of Molecular Biomechanics, School of Life Science, the Graduate University for Advanced Studies, 444-8585, Okazaki, Japan
    Makoto Matsui & Yoshinori Ohsumi
  7. Department of Bioregulation and Metabolism, Tokyo Metropolitan Institute of Medical Science, 113-8613, Tokyo, Japan
    Akiko Kuma, Makoto Matsui & Noboru Mizushima
  8. Department of Bio-Science, Nagahama Institute of Bio-Science and Technology, Nagahama, 526-0829, Japan
    Akitsugu Yamamoto
  9. Department of Cell Genetics, National Institute of Genetics, Mishima, 411-8540, Japan
    Tamotsu Yoshimori

Authors

  1. Akiko Kuma
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  2. Masahiko Hatano
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  3. Makoto Matsui
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  4. Akitsugu Yamamoto
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  5. Haruaki Nakaya
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  6. Tamotsu Yoshimori
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  7. Yoshinori Ohsumi
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  8. Takeshi Tokuhisa
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  9. Noboru Mizushima
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Correspondence toNoboru Mizushima.

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Kuma, A., Hatano, M., Matsui, M. et al. The role of autophagy during the early neonatal starvation period.Nature 432, 1032–1036 (2004). https://doi.org/10.1038/nature03029

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