Autophagy, a lysosome-mediated degradation process evolutionarily conserved from yeast to mammals, is essential for maintaining cellular homeostasis and combating diverse cellular stresses. Autophagy activity is highly responsive to environmental changes and cellular perturbations. Biochemical and genomic analyses have revealed that autophagy in yeast and transformed cell lines is modulated at multiple layers, including transcriptional and post-transcriptional regulation of autophagy gene mRNA levels, post-translational modifications (PTMs) of autophagy proteins, and assembly of autophagy protein complexes. Autophagy activity in multicellular organisms is systemically coordinated between different cells/tissues/organs to ensure the cellular homeostasis at an organismal level. The signaling molecules that non-autonomously regulate autophagy in long-range tissues remain elusive. I will talk about our progress in studying the mechanism by which neurons systemically control autophagy activity in the hypodermis, intestine and muscle under physiological and stress conditions in C. elegans.