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Nutrient-sensing enzymes key to starvation response and survival in newborn mammals
Date:12/23/2012

MIT and a Howard Hughes Medical Institute (HHMI) investigator. "A normal neonate animal within an hour after birth responds to that condition, but one with its RagA stuck 'on' doesn't, and it dies. It basically has a huge energetic and nutritional crisis because it can't make the adaption."

These striking results stunned Alejo Efeyan, a postdoctoral researcher in the Sabatini lab, and first author of the Nature that describes this work.

"We were surprised that there was no inhibition of this pathway independent of RagAthat there is no backup system," says Efeyan. "And that RagA is a more global nutrient sensor that goes beyond its known function as an amino acid sensor."

RagA's role as an amino acid sensor had been established in cultured cells by the Sabatini lab. Yet when Efeyan compared nutrient levels in fasting newborn RagA-active mice with those of fasting pups with normal RagA, not only amino acids were reduced in RagA-active animals, also glucose levels were dangerously low. The animals were unable to "sense" either of these reductions, so autophagy failed to initiate in the RagA-active pups, which all died within hours of birth.

This newly identified function for RagA suggests much remains unknown about the cell biology of nutrient sensing, an area of research that Sabatini and his lab continue to investigate.


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Contact: Nicole Rura
rura@wi.mit.edu
617-258-6851
Whitehead Institute for Biomedical Research
Source:Eurekalert

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