title: Stoichiometry of STAT3 and mitochondrial proteins: Implications for the regulation of oxidative phosphorylation by protein-protein interactions.
abstract: The signal transducer and activator of transcription 3 (STAT3) is a transcription factor and downstream product of cytokine and growth factor pathways. Among members of the STAT family, STAT3 has garnered particular interest due to its role in cancer and development. Recently, it was proposed that STAT3 regulates cardiac ATP generation in vivo through protein interaction with the mitochondrial complexes of oxidative phosphorylation, specifically Complexes I/II. For this mechanism to work effectively, the cellular ratio of Complexes I/II and STAT3 must approach one. However, using three different proteomic approaches in cardiac tissue, we determined the ratio of Complexes I/II and STAT3 to be approximately 10(5). This finding suggests that direct protein interaction between Complexes I/II and STAT3 cannot be required for optimal ATP production, nor can it dramatically modulate oxidative phosphorylation in vivo. Thus, STAT3 is likely altering mitochondrial function via transcriptional regulation or indirect signaling pathways that warrant further investigation.
authors.affiliation: Laboratory of Cardiac Energetics, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Darci
authors.initials: D
authors.lastname: Phillips
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Reilley
authors.forename: Angel M
authors.initials: AM
authors.lastname: Aponte
authors.forename: Guanghui
authors.initials: G
authors.lastname: Wang
authors.forename: Emily
authors.initials: E
authors.lastname: Boja
authors.forename: Marjan
authors.initials: M
authors.lastname: Gucek
authors.forename: Robert S
authors.initials: RS
authors.lastname: Balaban
mesh_terms: D000818:Animals; D003576:Electron Transport Complex IV / Q000378:metabolism; D004734:Energy Metabolism; D005786:Gene Expression Regulation; D013058:Mass Spectrometry / Q000379:methods; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000378:metabolism; D010100:Oxygen / Q000737:chemistry*; D010766:Phosphorylation; D025941:Protein Interaction Mapping; D040901:Proteomics / Q000379:methods; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D013552:Swine; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D050796:STAT3 Transcription Factor; D014157:Transcription Factors; D003576:Electron Transport Complex IV; D010100:Oxygen