中国科学院昆明动物研究所机构知识库

The primary function of the nucleolus is ribosome biogenesis, which is an extremely ener-getically expensive process. Failures in ribosome biogenesis cause nucleolar stress with analtered energy status. However, little is known about the underlying mechanism linkingnucleolar stress to energy metabolism. Here we show that nucleolar stress is triggered byinactivation 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 processingor inhibition of rDNA transcription by actinomycin D (AD), leading to excessive lipid accu-mulation in Caenorhabditis elegans. The transcription factor PHA-4/FoxA acts as a sensor ofnucleolar 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-acyl-transferase 2), consequently promoting lipid accumulation. Importantly, inactivation of pha-4or dgat-2 is sufficient to abolish nucleolar stress-induced lipid accumulation and prolongedstarvation survival. The results revealed a distinct PHA-4-mediated lipogenesis pathway thatsenses nucleolar stress and shifts excessive energy for storage as fat.