@article{92113c68a7e34a29a9cd6e8ef9de0c72,
title = "Quantitative subcellular acyl-CoA analysis reveals distinct nuclear metabolism and isoleucine-dependent histone propionylation",
abstract = "Quantitative subcellular metabolomic measurements can explain the roles of metabolites in cellular processes but are subject to multiple confounding factors. We developed stable isotope labeling of essential nutrients in cell culture-subcellular fractionation (SILEC-SF), which uses isotope-labeled internal standard controls that are present throughout fractionation and processing to quantify acyl-coenzyme A (acyl-CoA) thioesters in subcellular compartments by liquid chromatography-mass spectrometry. We tested SILEC-SF in a range of sample types and examined the compartmentalized responses to oxygen tension, cellular differentiation, and nutrient availability. Application of SILEC-SF to the challenging analysis of the nuclear compartment revealed a nuclear acyl-CoA profile distinct from that of the cytosol, with notable nuclear enrichment of propionyl-CoA. Using isotope tracing, we identified the branched chain amino acid isoleucine as a major metabolic source of nuclear propionyl-CoA and histone propionylation, thus revealing a new mechanism of crosstalk between metabolism and the epigenome.",
keywords = "acyl-CoA, branched chain amino acids, histone, internal standard, isoleucine, matrix effects, metabolomics, mitochondria, nucleus, propionylation, subcellular",
author = "Sophie Trefely and Katharina Huber and Joyce Liu and Michael Noji and Stephanie Stransky and Jay Singh and Doan, {Mary T.} and Lovell, {Claudia D.} and {von Krusenstiern}, Eliana and Helen Jiang and Anna Bostwick and Pepper, {Hannah L.} and Luke Izzo and Steven Zhao and Xu, {Jimmy P.} and Bedi, {Kenneth C.} and Rame, {J. Eduardo} and Bogner-Strauss, {Juliane G.} and Clementina Mesaros and Simone Sidoli and Wellen, {Kathryn E.} and Snyder, {Nathaniel W.}",
note = "Funding Information: N.W.S. was supported by R01GM132261 and P30ES013508. K.E.W. is supported by R01CA228339, R01DK116005, R01CA174761, and R01CA248315. S.T. was supported by the American Diabetes Association through post-doctoral fellowship 1-18-PDF-144 . K.H. and J.B.-S. were supported by the Austrian Science Fund grants FWF W1226 and FWF P27108 . C.D.L. is supported by NIH T32 GM07170 . L.I. was supported by T32 GM-07229 and 2-T32-CA-115299-13 . S.Z. was supported by F99CA222741 . S. Stransky and S. Sidoli are supported by the Leukemia Research Foundation (Hollis Brownstein New Investigator Research Grant), AFAR (Sagol Network GerOmic Award), Deerfield (Xseed award), the NIH P30 grant CA01333047 , and the shared instrument grant NIH 1 S10 OD030286-01 . We thank Dr. Kenneth B Margulies and the Gift of Life organization for allowing the use of human tissue for this project. Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",
year = "2022",
month = jan,
day = "20",
doi = "10.1016/j.molcel.2021.11.006",
language = "English",
volume = "82",
pages = "447--462.e6",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "2",
}