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- Title
PKG and NHR-49 signalling co-ordinately regulate short-term fasting-induced lysosomal lipid accumulation in C. elegans.
- Authors
Wen-ming HUANG; Zhao-yu LI; Yan-jun XU; Wei WANG; Mao-ge ZHOU; Peng ZHANG; Ping-sheng LIU; Tao XU; Zheng-xing WU
- Abstract
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.
- Subjects
CAENORHABDITIS elegans; NUCLEAR receptors (Biochemistry); CELLULAR signal transduction; BIOACCUMULATION; LYSOSOMES; CYTOPLASM
- Publication
Biochemical Journal, 2014, Vol 461, Issue 3, p509
- ISSN
0264-6021
- Publication type
Academic Journal
- DOI
10.1042/BJ20140191