Editors' ChoiceAUTOPHAGY

Eating Your Heart Out

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Science's STKE  04 Jan 2005:
Vol. 2005, Issue 265, pp. tw1
DOI: 10.1126/stke.2652005tw1

Kuma et al. have uncovered an intriguing role for autophagy--a stress response in which cells sequester and then cannibalize portions of their own cytoplasm--in the transition from survival as a fetus to neonatal life (see Heintz). Newborn mammals face many challenges: Among these is maintaining an adequate supply of nutrients during the interval between losing placental support and starting to nurse. Using a fluorescently labeled molecular marker for autophagosomes, Kumo et al. showed that, after birth, there was a dramatic increase in autophagy in mouse heart muscle and diaphragm (whose energy requirements rise after birth), as well as in alveolar cells and skin (whose external environment changes). This increase in autophagosome number was apparent within 30 min of birth, was maximal at 3 to 6 hours (by which time suckling had started), and subsided within a day or two. Mice lacking the gene encoding Atg5 (a protein required for autophagy) appeared nearly normal at birth but died sooner than wild-type mice under nonsuckling conditions. Plasma and tissue amino acid concentration of Atg–/– mice was normal at delivery but lower then that of wild-type mice by 10 hours. Further, the activity of the energy sensor AMP-activated kinase (AMPK) was stimulated by a 10-hour fast in Atg–/– mice, but not in wild-type mice, indicating an increase in the AMP:ATP ratio (and thus energy depletion). Thus, amino acid production through the autophagic pathway appears to play a key role in early energy homeostasis.

A. Kuma, M. Hatano, M. Matsui, A. Yamamoto, H. Nakaya, T. Yoshimori, Y. Ohsumi, T. Tokuhisa, N. Mizushima, The role of autophagy during the early neonatal starvation period. Nature 432, 1032-1036 (2004). [PubMed]

N. Heintz, Survival by self-digestion. Nature 432, 963 (2004). [PubMed]

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