The role of autophagy during the early neonatal starvation period.
At birth the trans-placental nutrient supply is suddenly interrupted, and neonates face severe starvation until supply can be restored through milk nutrients. 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. 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 (approximately 12 h) is much shorter than that of wild-type mice (approximately 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.
Kuma
Akiko
A
Time's Arrow and Biosignaling, PRESTO, Japan Science and Technology Agency, Kawaguchi 332-0012, Japan.
Hatano
Masahiko
M
Matsui
Makoto
M
Yamamoto
Akitsugu
A
Nakaya
Haruaki
H
Yoshimori
Tamotsu
T
Ohsumi
Yoshinori
Y
Tokuhisa
Takeshi
T
Mizushima
Noboru
N
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001343:Autophagy / Q000502:physiology*; D000071187:Autophagy-Related Protein 5; D002585:Cesarean Section; D004734:Energy Metabolism; D005260:Female; D017353:Gene Deletion; D006706:Homeostasis; D008247:Lysosomes / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D013217:Starvation / Q000378:metabolism*; D015996:Survival Rate; D013997:Time Factors
C495773:Atg5 protein, mouse; D000071187:Autophagy-Related Protein 5; D008869:Microtubule-Associated Proteins