title: Neuropeptide signals cell non-autonomous mitochondrial unfolded protein response.
abstract: Neurons have a central role in the systemic coordination of mitochondrial unfolded protein response (UPRmt) and the cell non-autonomous modulation of longevity. However, the mechanism by which the nervous system senses mitochondrial stress and communicates to the distal tissues to induce UPRmtremains unclear. Here we employ the tissue-specific CRISPR-Cas9 approach to disrupt mitochondrial function only in the nervous system of Caenorhabditis elegans, and reveal a cell non-autonomous induction of UPRmtin peripheral cells. We further show that a neural sub-circuit composed of three types of sensory neurons, and one interneuron is required for sensing and transducing neuronal mitochondrial stress. In addition, neuropeptide FLP-2 functions in this neural sub-circuit to signal the non-autonomous UPRmt. Taken together, our results suggest a neuropeptide coordination of mitochondrial stress response in the nervous system.
authors: State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China.
authors: Li-Wa
authors: LW
authors: Shao
authors: State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China.
authors: Rong
authors: R
authors: Niu
authors: State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China.
authors: Ying
authors: Y
authors: Liu
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified / Q000378:metabolism; D064113:CRISPR-Cas Systems / Q000235:genetics; D017173:Caenorhabditis elegans / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D018390:Gene Targeting; D005838:Genotype; D007413:Intestinal Mucosa / Q000378:metabolism; D008136:Longevity; D008928:Mitochondria / Q000378:metabolism*; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D015398:Signal Transduction; D056811:Unfolded Protein Response / Q000502:physiology*; D020692:rab3 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; C583030:Flp-2 protein, C elegans; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; C098176:UNC-119 protein, C elegans; D020692:rab3 GTP-Binding Proteins