A C9orf72-CARM1 axis regulates lipid metabolism under glucose starvation-induced nutrient stress [Research Papers]

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.

Source: Genes and Development - November 1, 2018 Category: Genetics & Stem Cells Authors: Liu, Y., Wang, T., Ji, Y. J., Johnson, K., Liu, H., Johnson, K., Bailey, S., Suk, Y., Lu, Y.-N., Liu, M., Wang, J. Tags: Research Papers Source Type: research