Dec.
23, 2012 — In the perilous hours immediately after birth, a newborn mammal
must survive the sudden loss of food supply from its mother. Under normal
circumstances, newborns mount a metabolic response to ward off starvation until
feeding occurs. This survival response involves a process of controlled
breakdown of internal energetic sources known as autophagy. Although autophagy
has been well documented, the key mechanistic regulators of autophagy in vivo
have remained poorly understood.
Whitehead
Institute researchers have discovered that a family of nutrient-sensing
enzymes, dubbed Rag GTPases, modulates the activity of the mTORC1 protein
complex, whose inhibition is essential for autophagy and survival in newborns.
The finding, reported this week in the journal Nature, emerges from the
lab of Whitehead Member David Sabatini, whose earlier in vitro studies showed
that mTORC1 (for "mechanistic target of rapamycin complex 1") senses
the presence of vital amino acids via interactions with Rag GTPases.
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