Proteolytic activation of fatty acid synthase signals pan-stress resolution.

"data availability the mrna-seq data generated in this study have been deposited in the gene expression omnibus database under accession code gse226048 . to reveal the metabolic impact of ced-3 caspase on fasn-1 we used untargeted metabolomics in c elegans to analyse the profiles of wild-type ced-3(-) and fasn-1(d/e) strains in normal and stress conditions (supplementary data 1 ).; to further investigate the impact of fasn-ctf on gene expression we performed mrna-seq analysis (supplementary data 2 ).; we also analysed the metabolic impact of expressing fasn-ctf on ced-3(-) and wild-type animals under er stress using targeted metabolomics (supplementary data 3 and extended data fig 8fg ).; statistical analyses and p values are provided in figures legends supplementary data 1-3 and source data.; supplementary data 1 untargeted metabolomics for wild-type ced-3(-) and fasn-1(d/e) with no stress er osmotic and ros stress.; supplementary data 2 mrna-seq differential expression of ced-3(-) with or without fasn-ctf expression under er stress.; supplementary data 3 targeted metabolomics for wild-type and ced-3(-) with or without fasn-ctf expression under er stress. data availability the mrna-seq data generated in this study have been deposited in the gene expression omnibus database under accession code gse226048"

"Competing interests R.J.D. is a founder and advisor for Atavistik Bioscience and an advisor for Agios Pharmaceuticals, Vida Ventures and Droia Ventures. The other authors declare no competing interests."

"We thank D. Mangelsdorf, S. Kliewer, D. Pan, M. Cobb, J. Goodman, E. Ross, M. Henne, M. Reese, J. Collins and all members of the Weaver laboratory for helpful discussions; G. Wendt in the Collins laboratory for assistance with confocal microscopy; the CGC (funded by the National Institutes of Health (NIH) Office of Research Infrastructure Programs; P40 OD010440) for materials; and WormBase, MetaboAnalyst, SMPDB, WormCat and UniProt databases. A targeted metabolomics screen was provided by the CRI Metabolomics Core. mRNA-seq was performed by the McDermott Center Sequencing Core and data analysis was provided by the McDermott Center Bioinformatics Laboratory. Protein mass spectrometry was performed and analysed by the UTSW Proteomics Core facility. We thank A. Lemoff for help with peak identification. This work is supported by Welch Foundation grant I-2022-20190330 (B.P.W.); NIH grants R35GM133755 (B.P.W.), 2-R35CA220449-07 (R.J.D.), R01AG067604 (M.S.), R01AR076325 (C.M.K.) and R01AR071967 (C.M.K.); and investigator funding through HHMI (R.J.D.). The funders had no role in study design, data acquisition, decision to publish or preparation of the paper. Author contributions: Conceptualization was the responsibility of H.W., Y.M.W. and B.P.W. Methodology and investigation were the responsibility of H.W., Y.M.W., C.Y., Y.Z., G.H., M.S., C.M.K. and B.P.W. Formal analysis was conducted by H.W., Y.M.W., C.Y., Y.Z., G.H., M.S., C.M.K., R.J.D. and B.P.W. Writing was carried out by H.W., Y.M.W., R.J.D. and B.P.W. Supervision of the study was carried out by Y.M.W., R.J.D. and B.P.W. Funding acquisition was the responsibility of R.J.D., C.M.K., M.S. and B.P.W."