title: A Transcript-Specific eIF3 Complex Mediates Global Translational Control of Energy Metabolism.
abstract: The multi-subunit eukaryotic translation initiation factor eIF3 is thought to assist in the recruitment of ribosomes to mRNA. The expression of eIF3 subunits is frequently disrupted in human cancers, but the specific roles of individual subunits in mRNA translation and cancer remain elusive. Using global transcriptomic, proteomic, and metabolomic profiling, we found a striking failure of Schizosaccharomyces pombe cells lacking eIF3e and eIF3d to synthesize components of the mitochondrial electron transport chain, leading to a defect in respiration, endogenous oxidative stress, and premature aging. Energy balance was maintained, however, by a switch to glycolysis with increased glucose uptake, upregulation of glycolytic enzymes, and strict dependence on a fermentable carbon source. This metabolic regulatory function appears to be conserved in human cells where eIF3e binds metabolic mRNAs and promotes their translation. Thus, via its eIF3d-eIF3e module, eIF3 orchestrates an mRNA-specific translational mechanism controlling energy metabolism that may be disrupted in cancer.
authors.affiliation: Tumor Initiation and Maintenance Program, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Meera
authors.initials: M
authors.lastname: Shah
authors.affiliation: School of Pharmaceutical Sciences and Center for Stress Signaling Networks, Xiamen University, Xiang'An South Road, Xiamen 361102, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Su
authors.affiliation: Tumor Initiation and Maintenance Program, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Judith S
authors.initials: JS
authors.lastname: Scheliga
authors.affiliation: G0 Cell Unit, Okinawa Institute of Science and Technology Graduate University, 1919-1 Tancha, Onna-son, Okinawa 904-0495, Japan.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Pluskal
authors.affiliation: Universitat Pompeu Fabra, Calle Doctor Aiguader 88, 08003 Barcelona, Spain.
authors.forename: Susanna
authors.initials: S
authors.lastname: Boronat
authors.affiliation: Proteomics Facility, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Khatereh
authors.initials: K
authors.lastname: Motamedchaboki
authors.affiliation: Proteomics Facility, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Alexandre Rosa
authors.initials: AR
authors.lastname: Campos
authors.affiliation: Applied Bioinformatics Core, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Feng
authors.initials: F
authors.lastname: Qi
authors.affiliation: Universitat Pompeu Fabra, Calle Doctor Aiguader 88, 08003 Barcelona, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Hidalgo
authors.affiliation: G0 Cell Unit, Okinawa Institute of Science and Technology Graduate University, 1919-1 Tancha, Onna-son, Okinawa 904-0495, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Yanagida
authors.affiliation: Tumor Initiation and Maintenance Program, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA; School of Pharmaceutical Sciences and Center for Stress Signaling Networks, Xiamen University, Xiang'An South Road, Xiamen 361102, China; San Diego Center for Systems Biology, La Jolla, CA 92093, USA. Electronic address: dwolf@sbpdiscovery.org.
authors.forename: Dieter A
authors.initials: DA
authors.lastname: Wolf
mesh_terms: D045744:Cell Line, Tumor; D045222:Electron Transport Chain Complex Proteins / Q000172:deficiency / Q000235:genetics; D039621:Eukaryotic Initiation Factor-3 / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006019:Glycolysis / Q000235:genetics*; D006801:Humans; D061986:MCF-7 Cells; D055442:Metabolome; D010085:Oxidative Phosphorylation; D014176:Protein Biosynthesis; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D012270:Ribosomes / Q000235:genetics / Q000378:metabolism; D012568:Schizosaccharomyces / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D059467:Transcriptome
chemical_list: D045222:Electron Transport Chain Complex Proteins; D039621:Eukaryotic Initiation Factor-3; D021122:Protein Subunits; D012333:RNA, Messenger