RRC ID 2392
Author Kuma A, Hatano M, Matsui M, Yamamoto A, Nakaya H, Yoshimori T, Ohsumi Y, Tokuhisa T, Mizushima N.
Title The role of autophagy during the early neonatal starvation period.
Journal Nature
Abstract 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.
Volume 432(7020)
Pages 1032-6
Published 2004-12-23
DOI 10.1038/nature03029
PII nature03029
PMID 15525940
MeSH Animals Animals, Newborn / metabolism* Autophagy / physiology* Autophagy-Related Protein 5 Cesarean Section Energy Metabolism* Female Gene Deletion Homeostasis Lysosomes / metabolism Mice Mice, Knockout Mice, Transgenic Microtubule-Associated Proteins / deficiency Microtubule-Associated Proteins / genetics Microtubule-Associated Proteins / metabolism* Pregnancy Starvation / metabolism* Survival Rate Time Factors
IF 42.779
Times Cited 2003
Mice RBRC00806