Starvation Response in Caenorhabditis elegans
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When the supply of environmental nutrients is limited, multicellular animas can make physiological and behavioral changes so as to cope with nutrient starvation. Although starvation response is essential for the survival of animals during nutrient deprivation, uncontrolled or uncoordinated starvation responses could be harmful. Autophagy, a lysosomal degradation pathway for long-lived proteins and cytoplasmic organelles, is known to be an important starvation response, which promotes both cell and organism survival by providing fundamental building blocks to maintain energy homeostasis during starvation. Under different conditions, however, autophagy may instead act to promote cell death through an autophagic cell death pathway. Why autophagy acts in some instances to promote survival but in others to promote death is poorly understood. Here I show that physiological levels of autophagy act to promote survival in Caenorhabditis elegans during starvation, whereas insufficient or excessive levels of autophagy contribute to death. I find that inhibition of autophagy decreases survival of wild-type worms during starvation. Furthermore, I find that in gpb-2 starvation-hypersensitive mutants, starvation induces excessive autophagy in pharyngeal muscles, which in turn, causes damage that may contribute to death. These results demonstrate that, depending on level of its activation, autophagy can have either prosurvival or prodeath functions, providing in vivo evidence that an uncontrolled starvation response could be harmful to animals. Thus, it is important that animals ensure that their starvation response is coordinated between individual cells. However, the mechanisms by which animals sense starvation systemically remain elusive. Here I use gpb-2 mutants to identify molecules and mechanisms that modulate starvation signaling. I found that specific amino acids could suppress the starvation-induced death of gpb-2 mutants, and that MGL-1 and MGL-2, C. elegans homologs of metabotropic glutamate receptors, were involved. MGL-1 and MGL-2 acted in AIY and AIB neurons respectively. Treatment with leucine suppressed starvation-induced stress resistance and life span extension in wild-type worms, and mutation of mgl-1 and mgl-2 abolished these effects of leucine. Theses results suggest that metabotropic glutamate receptor homologs in AIY and AIB neuron may modulate a systemic starvation response in C. elegans.