Reference - Detail
|Author||Huang WM, Li ZY, Xu YJ, Wang W, Zhou MG, Zhang P, Liu PS, Xu T, Wu ZX.|
|Title||PKG and NHR-49 signalling co-ordinately regulate short-term fasting-induced lysosomal lipid accumulation in C. elegans.|
Lysosomes act as terminal degradation organelles to hydrolyse macromolecules derived from both the extracellular space and the cytoplasm. In Caenorhabditis elegans fasting induces the lysosomal compartment to expand. However, the molecular and cellular mechanisms for this stress response remain largely unclear. In the present study, we find that short-term fasting leads to increased accumulation of polar lipids in lysosomes. The fasting response is co-ordinately regulated by EGL-4, the C. elegans PKG (protein kinase G) orthologue, and nuclear hormone receptor NHR-49. Further results demonstrate that EGL-4 acts in sensory neurons to enhance lysosomal lipid accumulation through inhibiting the DAF-3/SMAD pathway, whereas NHR-49 acts in intestine to inhibit lipids accumulation via activation of IPLA-2 (intracellular membrane-associated calcium-independent phospholipase A2) in cytoplasm and other hydrolases in lysosomes. Remarkably, the lysosomal lipid accumulation is independent of autophagy and RAB-7-mediated endocytosis. Taken together, our results reveal a new mechanism for lysosomal lipid metabolism during the stress response, which may provide new clues for investigations of lysosome function in energy homoeostasis.
|MeSH||Animals Animals, Genetically Modified Caenorhabditis elegans / enzymology Caenorhabditis elegans / genetics Caenorhabditis elegans / physiology* Caenorhabditis elegans / ultrastructure Caenorhabditis elegans Proteins / agonists Caenorhabditis elegans Proteins / antagonists & inhibitors Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cyclic GMP-Dependent Protein Kinases / genetics Cyclic GMP-Dependent Protein Kinases / metabolism* Enzyme Activation Fasting / adverse effects Hydrolases / chemistry Hydrolases / genetics Hydrolases / metabolism Kinetics Lipid Metabolism* Lysosomes / metabolism* Lysosomes / ultrastructure Mutation Nerve Tissue Proteins / agonists Nerve Tissue Proteins / antagonists & inhibitors Nerve Tissue Proteins / genetics Nerve Tissue Proteins / metabolism Phospholipases A2, Calcium-Independent / chemistry Phospholipases A2, Calcium-Independent / genetics Phospholipases A2, Calcium-Independent / metabolism RNA Interference Receptors, Cytoplasmic and Nuclear / genetics Receptors, Cytoplasmic and Nuclear / metabolism* Sensory Receptor Cells / enzymology Sensory Receptor Cells / metabolism Sensory Receptor Cells / ultrastructure Signal Transduction* Smad Proteins / antagonists & inhibitors Smad Proteins / genetics Smad Proteins / metabolism Stress, Physiological* Up-Regulation|
|WOS Category||BIOCHEMISTRY & MOLECULAR BIOLOGY|