title: Lipid droplet protein LID-1 mediates ATGL-1-dependent lipolysis during fasting in Caenorhabditis elegans.
abstract: Lipolysis is a delicate process involving complex signaling cascades and sequential enzymatic activations. In Caenorhabditis elegans, fasting induces various physiological changes, including a dramatic decrease in lipid contents through lipolysis. Interestingly, C. elegans lacks perilipin family genes which play a crucial role in the regulation of lipid homeostasis in other species. Here, we demonstrate that in the intestinal cells of C. elegans, a newly identified protein, lipid droplet protein 1 (C25A1.12; LID-1), modulates lipolysis by binding to adipose triglyceride lipase 1 (C05D11.7; ATGL-1) during nutritional deprivation. In fasted worms, lipid droplets were decreased in intestinal cells, whereas suppression of ATGL-1 via RNA interference (RNAi) resulted in retention of stored lipid droplets. Overexpression of ATGL-1 markedly decreased lipid droplets, whereas depletion of LID-1 via RNAi prevented the effect of overexpressed ATGL-1 on lipolysis. In adult worms, short-term fasting increased cyclic AMP (cAMP) levels, which activated protein kinase A (PKA) to stimulate lipolysis via ATGL-1 and LID-1. Moreover, ATGL-1 protein stability and LID-1 binding were augmented by PKA activation, eventually leading to increased lipolysis. These data suggest the importance of the concerted action of lipase and lipid droplet protein in the response to fasting signals via PKA to maintain lipid homeostasis.
authors.affiliation: Department of Biological Sciences, Institute of Molecular Biology & Genetics, Seoul National University, Seoul, South Korea.
authors.forename: Jung Hyun
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Biological Sciences, Institute of Molecular Biology & Genetics, Seoul National University, Seoul, South Korea.
authors.forename: Jinuk
authors.initials: J
authors.lastname: Kong
authors.affiliation: Department of Biological Sciences, Institute of Molecular Biology & Genetics, Seoul National University, Seoul, South Korea.
authors.forename: Ju Yeon
authors.initials: JY
authors.lastname: Jang
authors.affiliation: Department of Biological Sciences, Institute of Molecular Biology & Genetics, Seoul National University, Seoul, South Korea.
authors.forename: Ji Seul
authors.initials: JS
authors.lastname: Han
authors.affiliation: Department of Biological Sciences, Institute of Molecular Biology & Genetics, Seoul National University, Seoul, South Korea.
authors.forename: Yul
authors.initials: Y
authors.lastname: Ji
authors.affiliation: Department of Biological Sciences, Institute of Molecular Biology & Genetics, Seoul National University, Seoul, South Korea Department of Biophysics and Chemical Biology, Seoul National University, Seoul, South Korea.
authors.forename: Junho
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Biological Sciences, Institute of Molecular Biology & Genetics, Seoul National University, Seoul, South Korea jaebkim@snu.ac.kr.
authors.forename: Jae Bum
authors.initials: JB
authors.lastname: Kim
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D005215:Fasting; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000166:cytology; D008049:Lipase / Q000378:metabolism*; D066292:Lipid Droplets / Q000378:metabolism; D008066:Lipolysis; D015398:Signal Transduction
chemical_list: D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; C000595117:lipid droplet protein 1, C elegans; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; C534632:ATGL-1 protein, C elegans; D008049:Lipase