Genome-wide RNAi Screen for Fat Regulatory Genes in C. elegans Identifies a Proteostasis-AMPK Axis Critical for Starvation Survival

• DOI: 10.1016/j.celrep.2017.06.068
• Publication Date: 2017-07-18T22:46:59Z
• Authors: Christopher M. We...; Elizabeth C. Pino; Christopher E. Carr; Lianfeng Wu; Ben Zhou; Lucydalila Cedillo; Michael C. Kacergis; Sean P. Curran; Alexander A. Soukas
• Keywords: Proteostasis; AMP-Activated Protein Kinase; Starvation response; Synthetic Lethality

Organisms must execute metabolic defenses to survive nutrient deprivation. We performed a genome-wide RNAi screen in Caenorhabditis elegans identify fat regulatory genes indispensable for starvation resistance. Here, we show that opposing proteostasis pathways are principal determinants of survival. Reduced function cytoplasmic aminoacyl tRNA synthetases (ARS genes) increases mass and extends survival, whereas reduced proteasomal reduces These converge on AMP-activated protein kinase (AMPK) as the critical effector defenses. Extended survival ARS deficiency is dependent upon increased proteasome-mediated activation AMPK. When proteasome inhibited, neither nor can fully activate AMPK, leading greatly diminished Thus, activity AMPK mechanistically linked highly correlated with Conversely, aberrant proteostasis-AMPK axis during nutritional excess may have implications obesity cardiometabolic diseases.