Newswise — For those who believe that teenagers are the hungriest people on earth, Noboru Mizushima of Japan's Tokyo Metropolitan Institute of Medical Science has disturbing news—babies are born starving. This is no metaphor. Neonates are so hungry that they start eating themselves or, at least, newborn lab mice 'eat' their own cells in the first three to 12 hours after birth to tide them over.
Mammalian cells have an ancient starvation response called autophagy. However until Mizushima developed a special transgenic mouse whose cells express a fluorescent marker for the process, we didn't have a good picture of how autophagy operates over a lifespan. In work just published in Nature, Mizushima reports that autophagy is a vital survival mechanism for mammals at birth, and in later life allows rapid response to food withdrawal.
(See a video at http://www.ascb.org/publicpolicy/pressbooks/pressbook04.html.)
Autophagy is the primary means for degrading materials within cells. Autophagy is needed to remodel organisms as they grow, resist disease and respond to stresses like starvation. Cytoplasmic materials are enwrapped and sequestered by autophagosomal membranes, which subsequently fuse with lysosomes where their contents are degraded and nutrients liberated. Mizushima's lab made a transgenic mouse that expresses a fluorescent autophagosome marker (GFP-LC3). This marker provides an accurate indicator of autophagy activity in many kinds of tissue and every developmental stage from embryo to adult. The lab also developed an autophagy-defective Atg5 knockout mouse.
Autophagy activity is generally low in embryos, but immediately after birth, it rises sharply in various organs including the heart, diaphragm, lung and skin. Neonatal autophagy levels remain high for 3-12 hours, then return to basal levels within a day or two. The autophagy-defective knockouts appear almost normal at birth but then die within one day, suggesting that neonates depend on autophagy to provide nutrients immediately after birth. Supporting this idea, forced milk feeding can prolong their survival. Without forced feeding, the Atg5 knockout newborns had reduced amino acid levels in their plasma and tissues, plus many signs of energy depletion. Similarly, in autophagy-tagged young adult mice, food withdrawal triggered rapid increases in autophagy in a variety of tissues.
Starvation (or the threat of starvation) is a fact of life for nearly all creatures. For mammals, birth is a time of inescapable starvation. The supply of nutrients across the placenta suddenly stops at birth, and while 'colostrum' is available immediately from the mother's breasts, real milk production does not begin until 2-5 days later. Until milk arrives and the neonate figures out how to get it, newborn mammals must fall back on autophagic degradation of their own proteins. "We must eat ourselves to survive," says Mizushima.
Role of Mammalian Autophagy as a Starvation Response, N. Mizushima1,2 ; 1 Department of Bioregulation and Metabolism, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan, 2 Japan Science and Technology Agency, Kawaguchi, Japan.
At the ASCB Meeting: Session 374, Minisymposium 21: Autophagy & Organelle Turnover, Room 147 Author presents: Tuesday, Dec. 7, 3:40 PM—5:45 PM.
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