Inherent electrochemical activity of extrachromosomal DNA hub shapes spatial redox environment in nucleus.

Extrachromosomal DNA (ecDNA) hubs create an active electrochemical environment that non-enzymatically reduces oxidized glutathione (GSSG) to GSH, forming a protective GSH cloud that shields ecDNA from damage and sustains oncogene expression. Spermidine, which disrupts the ecDNA hub interfacial environment, breaks this redox balance and drives tumor death. The work was done with metabolomics, biochemistry, and imaging in human cancer cells and mouse models.