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论文题目: PHA-4/FoxA Senses Nucleolar Stress to Regulate Lipid Accumulation in Caenorhabditis Elegans
作者: Wu J, Jiang X, Li Y, Zhu T, Zhang J, Zhang Z, Zhang L, Zhang Y, Wang Y, Zou X, Liang B
联系作者: liangb@mail.kiz.ac.cn
发表年度: 2018
DOI: doi: 10.1038/s41467-018-03531-2
摘要:

The primary function of the nucleolus is ribosome biogenesis, which is an extremely energetically expensive process. Failures in ribosome biogenesis cause nucleolar stress with an altered energy status. However, little is known about the underlying mechanism linking nucleolar stress to energy metabolism. Here we show that nucleolar stress is triggered by inactivation of RSKS-1 (ribosomal protein S6 kinase), RRP-8 (ribosomal RNA processing 8), and PRO-2/3 (proximal proliferation), all of which are involved in ribosomal RNA processing or inhibition of rDNA transcription by actinomycin D (AD), leading to excessive lipid accumulation in Caenorhabditiselegans. The transcription factor PHA-4/FoxA acts as a sensor of nucleolar stress to bind to and transactivate the expression of the lipogenic genes pod-2 (acetyl-CoA carboxylase), fasn-1 (fatty acid synthase), and dgat-2 (diacylglycerol O-acyltransferase 2), consequently promoting lipid accumulation. Importantly, inactivation of pha-4 or dgat-2 is sufficient to abolish nucleolar stress-induced lipid accumulation and prolonged starvation survival. The results revealed a distinct PHA-4-mediated lipogenesis pathway that sensesnucleolar stress and shifts excessive energy for storage as fat

刊物名称: Nature Communications
论文出处: https://www.nature.com/articles/s41467-018-03531-2
影响因子: 12.124(2016年)