Stoichiometry of STAT3 and mitochondrial proteins: Implications for the regulation of oxidative phosphorylation by protein-protein interactions.

The signal transducer and activator of transcription 3 is a transcription factor and downstream product of cytokine and growth factor pathways. Among members of the family, has garnered particular interest due to its role in cancer and development. Recently, it was proposed that duanyu18133 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 duanyu18133 must approach one. However, using three different proteomic approaches in cardiac tissue, we determined the ratio of Complexes I/II and duanyu18133 to be approximately 10(5). This finding suggests that direct protein interaction between Complexes I/II and duanyu18133 cannot be required for optimal ATP production, nor can it dramatically modulate oxidative phosphorylation in vivo. Thus, duanyu18133 is likely altering mitochondrial function via transcriptional regulation or indirect signaling pathways that warrant further investigation.

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