A C9orf72-CARM1 axis regulates lipid metabolism under glucose starvation-induced nutrient stress
| Autor: | Yon Ju Ji, Scott Bailey, Kenji Johnson, Mingming Liu, Kaitlin Johnson, Hong-he Liu, Yu Ning Lu, Yongwon Suk, Yang Liu, Jiou Wang, Tao Wang |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Protein-Arginine N-Methyltransferases CARM1 Biology 03 medical and health sciences chemistry.chemical_compound Mice C9orf72 Stress Physiological Genetics medicine Animals Humans Epigenetics Amyotrophic lateral sclerosis Fatty acid synthesis Cells Cultured NADPH oxidase C9orf72 Protein Autophagy Amyotrophic Lateral Sclerosis Fatty Acids Lipid metabolism medicine.disease Lipid Metabolism Cell biology 030104 developmental biology Glucose HEK293 Cells chemistry Frontotemporal Dementia biology.protein Commentary Lysosomes Developmental Biology |
| Zdroj: | Genesdevelopment. 32(21-22) |
| ISSN: | 1549-5477 |
| Popis: | Cells undergo metabolic adaptation during environmental changes by using evolutionarily conserved stress response programs. This metabolic homeostasis is exquisitely regulated, and its imbalance could underlie human pathological conditions. We report here that C9orf72, which is linked to the most common forms of the neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), is a key regulator of lipid metabolism under stress. Loss of C9orf72 leads to an overactivation of starvation-induced lipid metabolism that is mediated by dysregulated autophagic digestion of lipids and increased de novo fatty acid synthesis. C9orf72 acts by promoting the lysosomal degradation of coactivator-associated arginine methyltransferase 1 (CARM1), which in turn regulates autophagy–lysosomal functions and lipid metabolism. In ALS/FTD patient-derived neurons or tissues, a reduction in C9orf72 function is associated with dysregulation in the levels of CARM1, fatty acids, and NADPH oxidase NOX2. These results reveal a C9orf72–CARM1 axis in the control of stress-induced lipid metabolism and implicates epigenetic dysregulation in relevant human diseases. |
| Databáze: | OpenAIRE |
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